{"gene":"RAB27B","run_date":"2026-04-28T19:45:45","timeline":{"discoveries":[{"year":2009,"finding":"RAB27B controls MVE (multivesicular endosome) docking at the plasma membrane; Rab27b silencing redistributes MVEs toward the perinuclear region, distinct from Rab27a which controls MVE size. The Rab27b effector Slac2b (EXPH5) phenocopies Rab27b silencing and inhibits exosome secretion.","method":"RNAi screen in HeLa cells; siRNA silencing; fluorescence microscopy of MVE localization; exosome quantification","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 2 — systematic RNAi screen with multiple orthogonal readouts, replicated with effector knockdown, highly cited foundational study","pmids":["19966785"],"is_preprint":false},{"year":2007,"finding":"Rab27b is required for regulated secretion and correct number of platelet dense granules; Rab27b KO mice exhibit hemorrhagic disease, impaired platelet aggregation, reduced dense granule secretion, and ~50% reduction in dense granule number per platelet. Rab27a partially compensates for the secretory defect but not the reduced granule number.","method":"Rab27b knockout mouse generation; crossed with Rab27a ashen KO to produce double KO; in vitro platelet aggregation assays; dense granule secretion assays; electron microscopy","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 — genetic KO mouse with multiple orthogonal functional readouts, replicated in double KO","pmids":["17384153"],"is_preprint":false},{"year":2004,"finding":"Rab27B localizes to amylase-containing secretory granules in rat parotid acinar cells and forms a complex with the effector Slac2-c/MyRIP on secretory granules in vivo. Disruption of the Rab27B–Slac2-c complex (by recombinant Slp homology domain or blocking antibodies) strongly inhibits isoproterenol-stimulated amylase release.","method":"Subcellular fractionation; immunoprecipitation; immunohistochemistry; functional blocking with recombinant protein and antibodies in streptolysin O-permeabilized cells","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods including Co-IP, localization, and functional inhibition assay with mechanistic specificity","pmids":["15039459"],"is_preprint":false},{"year":2007,"finding":"Rab27b is expressed in a wide range of exocytic cells and is involved in delivering secretory granules near the plasma membrane (the exocytic site). In pituitary double Rab27a/Rab27b KO mice, polarized distribution of secretory granules close to the plasma membrane is markedly impaired.","method":"LacZ knock-in reporter mouse for expression analysis; Rab27a/Rab27b double knockout mice generated by crossing; electron microscopy of secretory granule distribution in pituitary cells","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — genetic double KO model with direct ultrastructural readout of granule positioning","pmids":["17761531"],"is_preprint":false},{"year":2007,"finding":"Rab27b localizes to secretory granules in mast cells and is required for mast cell degranulation (beta-hexosaminidase release) and passive cutaneous anaphylaxis in vivo. Rab27b-deficient BMMC show ~10-fold increase in granules with fast microtubule-based movement, suggesting Rab27b regulates the transition from microtubule to actin-based granule motility.","method":"Rab27b KO and double KO mice; bone marrow-derived mast cell (BMMC) cultures; beta-hexosaminidase release assays; passive cutaneous anaphylaxis in vivo; live-cell time-lapse imaging; nocodazole treatment","journal":"Traffic (Copenhagen, Denmark)","confidence":"High","confidence_rationale":"Tier 2 — genetic KO with in vitro and in vivo functional readouts plus live-cell imaging mechanistic insight","pmids":["17587407"],"is_preprint":false},{"year":2002,"finding":"Rab27b associates with secretory granules and the effector granuphilin in pituitary endocrine cells (AtT20). Overexpression of inactive mutant Rab27b N133I significantly inhibits basal and forskolin-induced ACTH secretion.","method":"Subcellular fractionation; co-immunoprecipitation with granuphilin; dominant-negative overexpression; ACTH secretion assay","journal":"Endocrinology","confidence":"High","confidence_rationale":"Tier 2 — Co-IP plus dominant-negative functional assay with specific secretion readout","pmids":["11956164"],"is_preprint":false},{"year":2004,"finding":"Rab27b localizes to zymogen granule membranes in pancreatic acinar cells. Constitutively active Rab27b Q78L enhances CCK-induced amylase release by ~92%, while dominant-negative Rab27b N133I inhibits release by ~53%, demonstrating a role for Rab27b GTP/GDP cycling in pancreatic acinar exocytosis.","method":"Proteomics (MALDI-MS/MS) identification; Western blot and immunocytochemistry for localization; adenoviral overexpression of WT, Q78L, and N133I mutants; amylase secretion assay","journal":"Biochemical and biophysical research communications","confidence":"High","confidence_rationale":"Tier 1–2 — proteomic identification plus gain/loss-of-function mutagenesis with quantitative functional readout","pmids":["15451418"],"is_preprint":false},{"year":2003,"finding":"Rab27b localizes to alpha and dense granules in megakaryocytes. Inhibition of endogenous Rab27 function in primary megakaryocytes causes severe quantitative and qualitative defects in proplatelet formation. NF-E2 transcription factor is recruited to the Rab27B promoter and is required for its expression during terminal megakaryocyte differentiation.","method":"Immunofluorescence localization; dominant-negative Rab27 inhibition in primary megakaryocytes; chromatin immunoprecipitation (ChIP) for NF-E2 at Rab27B promoter; analysis of gunmetal mice","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 — ChIP demonstrating transcriptional regulation plus dominant-negative functional assay in primary cells","pmids":["12907454"],"is_preprint":false},{"year":2003,"finding":"Rab27b associates with the cytoplasmic face of fusiform vesicles in bladder urothelial umbrella cells and its expression is differentiation-dependent, suggesting a role in targeting uroplakins to the apical plasma membrane.","method":"Immuno-electron microscopy; Western blot comparing urothelial tissue vs. cultured cells; differentiation-dependent expression analysis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 — direct immuno-EM localization to specific vesicle type, but functional consequence inferred from correlative data","pmids":["14625374"],"is_preprint":false},{"year":2009,"finding":"Rab27a and Rab27b both regulate azurophilic granule exocytosis and NADPH oxidase recruitment to the plasma membrane in neutrophils via independent mechanisms. TIRF microscopy shows both isoforms are required for granule docking near the plasma membrane; upregulation of Rab27b in Rab27a-deficient cells does not compensate for the Rab27a secretory defect.","method":"Rab27a(ash/ash), Rab27b KO, and double KO mouse neutrophils; azurophilic granule exocytosis assays; TIRF microscopy of granule proximity to plasma membrane; NADPH oxidase activity assay","journal":"Traffic (Copenhagen, Denmark)","confidence":"High","confidence_rationale":"Tier 2 — genetic KO models with multiple orthogonal functional assays and direct imaging","pmids":["20028487"],"is_preprint":false},{"year":2010,"finding":"RAB27B promotes invasive growth of ER-positive breast cancer cells through GTP- and geranylgeranyl-dependent delivery of secretory vesicles. Mass spectrometry of RAB27B-positive vesicles identified HSP90α as a key cargo; RAB27B-dependent HSP90α secretion is required for MMP-2 activation and invasion.","method":"GFP-RAB27B overexpression; point mutants defective in GTP binding or geranylgeranylation; siRNA silencing; Matrigel and collagen invasion assays; mass spectrometry of purified RAB27B vesicles; orthotopic xenograft mouse model","journal":"Journal of the National Cancer Institute","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods including proteomics, mutagenesis, in vitro invasion, and in vivo xenograft with mechanistic follow-up","pmids":["20484105"],"is_preprint":false},{"year":2010,"finding":"Rab27b is an abundant synaptic vesicle Rab GTPase that, unlike Rab3a, persists on synaptic vesicle membranes upon Ca2+-triggered exocytosis and is resistant to GDI-mediated retrieval. Modulation of the Rab27b GTP/GDP switch impairs synaptic vesicle recycling.","method":"Quantitative mass spectrometry (iTRAQ) of synaptic vesicles; quantitative immunoblotting; fluorescence microscopy; GDI extraction assay; Rab27b GTP/GDP switch manipulation","journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience","confidence":"High","confidence_rationale":"Tier 1–2 — quantitative proteomics plus mechanistic GTP/GDP switch manipulation with functional readout","pmids":["20926670"],"is_preprint":false},{"year":2013,"finding":"In mast cells, Rab27a and Rab27b regulate distinct steps of degranulation: Rab27a/Mlph/MyoVa regulates cortical actin stability upstream of granule exocytosis, while Rab27b/Munc13-4 directly mediates granule exocytosis. Munc13-4-deficient mast cells phenocopy the Rab27b KO secretory impairment.","method":"Bone marrow-derived mast cells from multiple mutant mouse lines (ashen Rab27a, Rab27b KO, double KO, leaden Mlph KO, dilute MyoVa KO, jinx Munc13-4 KO); beta-hexosaminidase release assays; F-actin immunofluorescence; epistasis analysis","journal":"The FEBS journal","confidence":"High","confidence_rationale":"Tier 2 — genetic epistasis across multiple mutant lines with mechanistic pathway placement","pmids":["23281710"],"is_preprint":false},{"year":2011,"finding":"Rab27b regulates stimulation-dependent RANKL release from secretory lysosomes in osteoblastic cells. Suppression of Rab27b inhibits fusion of RANKL-containing lysosomal vesicles with the plasma membrane. The effectors Slp4-a, Slp5, and Munc13-4 coordinate Rab27a/b activity in this pathway; Munc13-4-deficient (jinx) mice show increased bone volume due to reduced osteoclast activity.","method":"siRNA knockdown of Rab27a, Rab27b, Slp4-a, Slp5, Munc13-4 in osteoblastic cells; RANKL release assays; immunofluorescence of vesicle localization; jinx mouse bone phenotype analysis","journal":"Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research","confidence":"High","confidence_rationale":"Tier 2 — RNAi epistasis with effector proteins plus in vivo genetic model with bone phenotype readout","pmids":["20939018"],"is_preprint":false},{"year":2007,"finding":"Crystal structure of mouse Rab27b-GDP reveals an open conformation with protruding switch and interswitch regions, stabilized through domain-swapping dimerization in the crystal. SAXS measurements show an extended monomer in solution, indicating highly flexible switch regions relevant to effector interaction.","method":"X-ray crystallography in three distinct crystal lattices; small-angle X-ray scattering (SAXS)","journal":"Acta crystallographica. Section D, Biological crystallography","confidence":"High","confidence_rationale":"Tier 1 — crystal structure determination with solution validation by SAXS","pmids":["17582168"],"is_preprint":false},{"year":2012,"finding":"The Rab27b effector Slac2-b (EXPH5) colocalizes with Rab27b and β4 integrin at early adhesion initiation sites in spreading keratinocytes. Loss-of-function of Slac2-b (frameshift mutation in humans or shRNA knockdown) causes keratinocyte adhesion disruption, cytoskeletal disruption, and increased perinuclear vesicles, establishing a role for the Rab27B–Slac2-b complex in keratinocyte biology.","method":"Whole-exome sequencing of human patients; immunofluorescence co-localization; shRNA knockdown in normal keratinocytes; cell adhesion assays","journal":"American journal of human genetics","confidence":"High","confidence_rationale":"Tier 2 — human loss-of-function mutation validated by shRNA model with orthogonal functional and localization readouts","pmids":["23176819"],"is_preprint":false},{"year":2011,"finding":"Rab27b is required for exocytosis of secretory vesicles in lacrimal gland acinar cells. Constitutively active Rab27b increases the average size of secretory vesicles while retaining subapical distribution; dominant-negative Rab27b redistributes Rab27b to cytoplasm. Rab27b KO and double KO mice (but not Rab27a ashen mice) show changes in abundance and organization of secretory vesicles. Disruption of actin filaments inhibits vesicle fusion to the apical membrane but not homotypic fusion.","method":"Confocal fluorescence microscopy; transmission electron microscopy of lacrimal gland from KO mice; constitutively active and dominant-negative Rab27b expression; syncollin-GFP secretory protein release assay; actin disruption experiments","journal":"American journal of physiology. Cell physiology","confidence":"High","confidence_rationale":"Tier 2 — genetic KO plus mutagenesis with multiple functional and ultrastructural readouts","pmids":["21525430"],"is_preprint":false},{"year":2013,"finding":"EPI64B (TBC1D10B) functions as a GTPase-activating protein (GAP) specific for Rab27B in pancreatic acinar cells. EPI64B overexpression almost completely abolishes GTP-Rab27b without affecting GTP-Rab3D, and enhances amylase release in a Rab27B-dependent manner. GAP-dead EPI64B mutations block these effects.","method":"Adenoviral overexpression in isolated pancreatic acini; GTP-bound Rab27B pulldown; amylase release assay; Rab27b KO mouse acini for epistasis; site-directed mutagenesis of catalytic residues","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 — enzymatic GAP activity demonstrated with mutagenesis and genetic epistasis in relevant cell type","pmids":["23671284"],"is_preprint":false},{"year":2002,"finding":"Rab27b dominant-negative mutants (T23N and N133I) fail to associate with melanosomes and cause redistribution of melanosomes from cell periphery to perinuclear region in melanocytes, implicating Rab27b in outward movement of melanosomes. Wild-type Rab27b co-localizes with TRP-1 and myosin Va at the cell periphery. Dominant-negative Rab27b also reduces dendrite number and length.","method":"GFP-tagged WT and dominant-negative Rab27b overexpression in melan-a melanocytes; confocal co-localization with TRP-1 and myosin Va; dendrite morphology analysis; intrinsic GTPase activity assay","journal":"The Journal of investigative dermatology","confidence":"Medium","confidence_rationale":"Tier 2 — dominant-negative approach with direct localization readout, but mechanistic specificity limited by dominant-negative artifacts","pmids":["12060386"],"is_preprint":false},{"year":2004,"finding":"Rab27b protein is present at extraordinary high levels (0.1% of total protein) on fusiform vesicles in bladder urothelium and is markedly reduced in cultured urothelial cells that fail to form fusiform vesicles, linking Rab27b expression to fusiform vesicle formation/maintenance.","method":"Immuno-electron microscopy; Western blot quantification; comparison of differentiated urothelium vs. de-differentiated cultured cells","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 — direct immuno-EM localization with quantitative expression correlation but no direct loss-of-function","pmids":["14625374"],"is_preprint":false},{"year":2008,"finding":"Slp1 (a Rab27 effector protein) interacts with Rab27B in vivo and co-localizes on zymogen granules in pancreatic acinar cells. Slp1 KO mice show increased number of zymogen granules, implicating the Rab27B–Slp1 complex in amylase secretion.","method":"Co-immunoprecipitation of Slp1 and Rab27B; co-localization by immunofluorescence; Slp1 KO mouse morphological analysis","journal":"Archives of biochemistry and biophysics","confidence":"Medium","confidence_rationale":"Tier 2 — Co-IP plus KO mouse phenotype, but functional measurement is morphological rather than direct secretion assay","pmids":["18477466"],"is_preprint":false},{"year":2016,"finding":"Kinesin-1 (Kif5b) is recruited to a Slp3/Rab27b effector complex on mast cell secretory granules in a PI3K-dependent and stimulus-dependent manner. PI3K-dependent formation of the kinesin-1/Slp3/Rab27b complex is required for microtubule-dependent movement of secretory granules toward the exocytic site during mast cell degranulation.","method":"Kif5b conditional KO mice; passive systemic anaphylaxis model; BMMC degranulation assays; SG translocation imaging; co-immunoprecipitation of kinesin-1/Slp3/Rab27b; PI3K inhibitor experiments","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 — genetic KO with Co-IP defining molecular complex and PI3K-dependence, in vitro and in vivo functional readouts","pmids":["27810912"],"is_preprint":false},{"year":2015,"finding":"Rab27b mediates shear stress-induced vesicular export of miR-143 from endothelial cells downstream of the KLF2 transcription factor. Rab7a and Rab27b are both required for this extracellular vesicle-based miRNA secretion pathway.","method":"Rab27b and Rab7a siRNA knockdown; shear stress stimulation; miR-143 vesicular export quantification in endothelial cells","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 3 — siRNA knockdown with functional secretion readout, single lab, single method","pmids":["26348397"],"is_preprint":false},{"year":2009,"finding":"After beta-adrenergic stimulation in parotid acinar cells, Rab27B translocates from secretory granules to the subapical region (5 min) and then dissociates into the cytosol (30 min) through binding to GDI (GDP dissociation inhibitor), which extracts GDP-bound Rab27B from membranes.","method":"Immunofluorescence time-course after isoproterenol treatment; subcellular fractionation; Rab27B-GDI complex detection in cytosol fractions","journal":"European journal of oral sciences","confidence":"Medium","confidence_rationale":"Tier 2 — direct localization tracking with mechanistic GDI coupling identified, single lab","pmids":["19583748"],"is_preprint":false},{"year":2012,"finding":"In lacrimal gland acinar cells, RAB27B enrichment occurs early in secretory vesicle formation at a basally-localized 'nascent vesicle site' adjacent to the trans-Golgi network. Transport from this nascent vesicle site to the subapical region requires intact microtubules. RAB27B-enriched vesicles in the subapical cytoplasm acquire Myosin 5C for actin-based motility.","method":"YFP-Rab27b live-cell confocal microscopy in rabbit lacrimal gland acinar cells; vesicle pool depletion-repletion protocol; nocodazole treatment; p150Glued co-localization; Myosin 5C co-localization","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 — live-cell imaging with functional perturbation revealing biogenesis mechanism, single lab","pmids":["22363735"],"is_preprint":false},{"year":2010,"finding":"Rab27b localizes to tubulovesicle membranes in gastric parietal cells. Upon stimulation, wild-type Rab27b and constitutively active Rab27b Q78L translocate to the apical membrane, while dominant-negative Rab27b N133I does not. Expression of Rab27b N133I almost completely inhibits acid secretion.","method":"Mass spectrometry identification in tubulovesicular fractions; YFP-tagged WT, Q78L, N133I adenoviral expression; fluorescence microscopy of resting and stimulated cells; aminopyrine accumulation acid secretion assay","journal":"Gastroenterology","confidence":"High","confidence_rationale":"Tier 1–2 — proteomic identification plus mutagenesis with quantitative functional secretion readout","pmids":["20888820"],"is_preprint":false},{"year":2004,"finding":"Rab27b is upregulated in Griscelli syndrome type II melanocytes (lacking Rab27a) and forms a tripartite complex with melanophilin and myosin Va transcripts containing exon F on the melanosome membrane, partially compensating for loss of Rab27a function.","method":"Real-time quantitative PCR; Western blot; immunofluorescence co-localization; yeast two-hybrid screening","journal":"Pigment cell research","confidence":"Medium","confidence_rationale":"Tier 2/3 — yeast two-hybrid plus immunofluorescence defining tripartite complex, but compensation is partial and mechanistic detail limited","pmids":["15357836"],"is_preprint":false},{"year":2017,"finding":"RAB27B controls stretch-induced exocytosis of discoidal/fusiform vesicles (DFVs) in bladder umbrella cells. RAB27A-specific shRNA does not inhibit exocytosis. RAB27B operates in a pathway parallel to and independent of the RAB11A-RAB8A-MYO5B pathway.","method":"Whole bladder filling preparation; shRNA-mediated knockdown of RAB27B and RAB27A; hGH-loaded DFV exocytosis assay; dominant-active/dominant-negative RAB11A and RAB8A mutants; Squassh segmentation quantification of RAB27B-positive DFVs","journal":"American journal of physiology. Cell physiology","confidence":"High","confidence_rationale":"Tier 2 — genetic loss-of-function with isoform specificity established, epistasis with parallel pathway demonstrated, ex vivo whole-organ functional assay","pmids":["29167152"],"is_preprint":false},{"year":2016,"finding":"Rab27b is required for lysosomal exocytosis and surface expression of proteolipid protein (PLP) in oligodendrocytes. Rab27b KD reduces lysosomal exocytosis, decreases PLP surface expression, and reduces myelin-like membrane formation in neuron co-culture.","method":"shRNA knockdown of Rab27b in oligodendrocytes; lysosomal exocytosis assays; PLP surface expression measurement; oligodendrocyte-neuron co-culture myelination assay","journal":"Neuroscience bulletin","confidence":"Medium","confidence_rationale":"Tier 2 — KD with multiple functional readouts, single lab","pmids":["27325508"],"is_preprint":false},{"year":2020,"finding":"Rab27b regulates alpha-synuclein release, autophagic clearance, and toxicity in neurons. Rab27b KD increases paracrine αsyn toxicity, shifts released αsyn to higher-molecular-weight species, increases insoluble intracellular αsyn, and impairs autophagic flux (reduced LC3 turnover after chloroquine treatment).","method":"shRNA knockdown; paracrine αsyn neuronal model; size-exclusion chromatography of released αsyn; immunofluorescence of LC3 puncta; chloroquine autophagic flux assay; Western blot of insoluble αsyn fractions","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal mechanistic readouts, single lab","pmids":["32350025"],"is_preprint":false},{"year":2023,"finding":"RAB27B controls NRAS palmitoylation and trafficking to the plasma membrane by interacting with ZDHHC9, a palmitoyl acyltransferase. RAB27B depletion selectively abrogates mutant NRAS-mediated ERK signaling and progenitor cell growth in mice, and reduces myelomonocytic leukemia development. RAB27B is upregulated in CBL- or JAK2-mutated myeloid malignancies.","method":"Proteomic studies; co-immunoprecipitation of RAB27B and ZDHHC9; Rab27b KO mice with NRAS mutant hematopoietic cells; NRAS palmitoylation assays; ERK signaling assays; in vivo leukemia model; primary human AML RAB27B depletion","journal":"The Journal of clinical investigation","confidence":"High","confidence_rationale":"Tier 2 — Co-IP defining interaction plus genetic KO in vivo model with multiple orthogonal mechanistic readouts","pmids":["37317963"],"is_preprint":false},{"year":2021,"finding":"NRF2 promotes Rab27b expression transcriptionally in urothelial cells, and RAB27B mediates NRF2-dependent UPEC expulsion from urothelial cells. Loss of NRF2 reduces RAB27B expression and impairs UPEC expulsion, increasing bacterial burden both in vitro and in vivo.","method":"NRF2 KO and overexpression in urothelial cells; RAB27B expression measurement; UPEC expulsion assays; mouse UTI model; dimethyl fumarate (NRF2 inducer) treatment","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 — genetic and pharmacological manipulation with in vitro and in vivo functional readouts, single lab","pmids":["34686330"],"is_preprint":false},{"year":2021,"finding":"FOXO1 transcriptionally regulates RAB27B expression in kidney proximal tubule cells. In high-glucose conditions (mimicking diabetic kidneys), FOXO1 is phosphorylated and inactivated, leading to RAB27B downregulation and decreased exosome secretion. Constitutively active nonphosphorylatable FOXO1 restores RAB27B and exosome secretion.","method":"Bioinformatics identification of FOXO1 binding sites in Rab27b promoter; high-glucose treatment of BUMPT cells; RAB27B overexpression rescue; constitutively active FOXO1 overexpression; diabetic mouse model exosome analysis","journal":"Diabetes","confidence":"Medium","confidence_rationale":"Tier 2 — promoter bioinformatics plus functional rescue experiments in vitro and in vivo mouse model, single lab","pmids":["33597203"],"is_preprint":false},{"year":2023,"finding":"CaSR activates RAB27B through a PI3K/PKA/mTOR/MADD (guanine nucleotide exchange factor) pathway, promoting secretion of cytokines (IL-6, IL-1β, IL-8, IP-10, RANTES) from breast cancer cells. Rab11A interacts with and activates MADD, a GEF for Rab27A/B, linking endocytic recycling endosomes to Rab27B-regulated secretory vesicles via endosomal PI3K (Vps34 and PI3KC2α).","method":"CaSR stimulation assays; PI3K/PKA/mTOR/MADD pharmacological inhibition; Co-immunoprecipitation of Rab11A and MADD; cytokine secretion ELISA; siRNA knockdown of pathway components","journal":"Cellular signalling","confidence":"Medium","confidence_rationale":"Tier 2 — Co-IP plus pharmacological dissection defining upstream activation pathway, single lab","pmids":["37604243"],"is_preprint":false},{"year":2020,"finding":"ZIP4 promotes RAB27B expression through CREB-regulated transcription in pancreatic cancer cells. RAB27B is required for the release of HSP70- and HSP90-associated extracellular vesicles that activate p38 MAPK and induce muscle-wasting gene expression (F-box protein 32, UBR2) in myotubes, causing myofibrillar protein loss and cachexia.","method":"ZIP4 shRNA knockdown; CREB inhibition; RAB27B expression measurement; EV isolation and Western blot; C2C12 myotube treatment with conditioned media/EVs; p38 MAPK activation assays; orthotopic pancreatic tumor mouse model","journal":"Gastroenterology","confidence":"Medium","confidence_rationale":"Tier 2 — genetic and pharmacological manipulation with mechanistic downstream readouts, in vitro and in vivo, single lab","pmids":["30342032"],"is_preprint":false},{"year":2013,"finding":"V-ATPase (vacuolar H+-ATPase) activity and subunits (V0a1, V0d1) are required for peripheral localization and size of Rab27B-positive secretory vesicles in breast cancer cells. Inhibition of V-ATPase reduces Rab27B-induced invasion, HSP90α secretion, and MMP-2 activation.","method":"Mass spectrometry of GFP-Rab27B vesicles identifying V-ATPase subunits; Western blot validation; bafilomycin A1 inhibition; siRNA knockdown of V0a1 and V0d1; invasion and secretion assays","journal":"International journal of cancer","confidence":"Medium","confidence_rationale":"Tier 2 — proteomics-driven discovery plus siRNA and pharmacological validation, single lab","pmids":["23390068"],"is_preprint":false},{"year":2019,"finding":"β-catenin/Tcf-4 transcriptional activation of RAB27B expression is required for secretion of exosomes from colorectal cancer stem cells. Exosomal miR-146a-5p cargo promotes stemness by targeting Numb in recipient cells.","method":"β-catenin/Tcf-4 transcription factor analysis; RAB27B knockdown; exosome secretion quantification; exosomal RNA sequencing; luciferase reporter and rescue assays","journal":"International journal of cancer","confidence":"Medium","confidence_rationale":"Tier 2 — transcription factor-driven RAB27B regulation with functional exosome secretion readout, single lab","pmids":["30980673"],"is_preprint":false},{"year":2012,"finding":"Rab27b negatively regulates c-kit surface expression in megakaryoblastic cells by promoting autocrine secretion of stem cell factor (SCF). Rab27b knockdown reduces SCF secretion, leading to reduced SCF-induced endolysosomal degradation of c-kit and thus increased c-kit surface expression.","method":"shRNA knockdown of Rab27b in CMK cells; c-kit surface expression measurement; SCF secretion assay; bafilomycin lysosome inhibition; flow cytometry","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 — KD with mechanistic dissection of ligand-receptor axis, single lab","pmids":["22349512"],"is_preprint":false},{"year":2025,"finding":"Rab27b promotes lysosomal function in neurons by supporting lysosomal enzyme maturation and acidic vesicle trafficking. Rab27b KO in neurons causes lysosomal proteolytic defects, enzymatic dysfunction, and exacerbated alpha-synuclein aggregation upon preformed fibril treatment. Rab27b overexpression enhances lysosomal activity and reduces insoluble αsyn accumulation.","method":"Rab27b KO mice; primary neuronal cultures; shRNA KD in αsyn-inducible neuronal model; lysosomal enzyme activity assays; lysosomal pH measurement; αsyn preformed fibril treatment; Rab27b overexpression; brain lysate analysis from postmortem human PD/DLB/iLBD tissue","journal":"The Journal of neuroscience : the official journal of the Society for Neuroscience","confidence":"High","confidence_rationale":"Tier 2 — genetic KO plus OE in multiple models with mechanistic lysosomal enzyme readouts and human tissue validation","pmids":["39965930"],"is_preprint":false},{"year":2024,"finding":"TGF-β suppresses RAB27B transcription via SMAD3, reducing exosome release from breast cancer cells. RAB27B depletion or TGF-β treatment increases quantity and alters protein composition of EVs, producing recomposed EVs that inhibit CD8+ T cell-mediated cancer killing.","method":"TGF-β treatment; SMAD3 identification as transcriptional repressor of RAB27B; click chemistry proteomics; RAB27B siRNA; exosome quantification; CD8+ T cell cytotoxicity assay","journal":"Journal of extracellular vesicles","confidence":"Medium","confidence_rationale":"Tier 2 — SMAD3-RAB27B transcriptional mechanism plus EV cargo proteomics with functional immune readout, single lab","pmids":["39723610"],"is_preprint":false},{"year":2020,"finding":"Rab27b KO in hippocampal mossy fiber (MF)-CA3 synapses completely eliminates long-term potentiation (LTP), an effect rescued by lentiviral re-expression of human Rab27b but not GFP. At SC-CA1 synapses, Rab27b KO increases facilitation. Rab27b and Rab3a act synergistically at presynaptic terminals for LTP expression.","method":"Rab27b KO mice; electrophysiology at SC-CA1 and DG-MF hippocampal synapses; frequency facilitation measurement; LTP induction; lentiviral rescue with human Rab27b","journal":"Physiological reports","confidence":"Medium","confidence_rationale":"Tier 2 — genetic KO with electrophysiological readouts and lentiviral rescue confirming specificity, single lab","pmids":["32358861"],"is_preprint":false},{"year":2016,"finding":"Genetic deletion of Rab27B in pancreatic acinar cells reduces the size of zymogen granules and moderately decreases digestive enzyme secretion, revealing a role in zymogen granule maturation distinct from Rab3D.","method":"Rab27B KO mouse model; electron microscopy of zymogen granule size; in vitro secretion assays from isolated acini; comparison with Rab3D","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 — genetic KO with ultrastructural and functional readouts, single lab","pmids":["26845357"],"is_preprint":false},{"year":2023,"finding":"KIAA1429 stabilizes RAB27B mRNA through the m6A/YTHDF1 axis in chronic myeloid leukemia cells, promoting RAB27B expression and leukemia cell proliferation and drug efflux. Inhibiting KIAA1429 reduces RAB27B mRNA stability, thereby sensitizing CML cells to imatinib.","method":"KIAA1429 knockdown; m6A modification analysis; YTHDF1 interaction; RAB27B mRNA stability assays; proliferation and apoptosis assays; drug resistance assays","journal":"Genes & diseases","confidence":"Medium","confidence_rationale":"Tier 3 — post-transcriptional regulation mechanism with functional readouts, single lab","pmids":["37692484"],"is_preprint":false},{"year":2025,"finding":"In neurons, Rab27b KO in A53T alpha-synuclein transgenic mice increases proteinase-K resistant αsyn and phospho-S129 αsyn in cortex, striatum, and substantia nigra, and increases astrocyte/microglial activation. In AAV αsyn model, Rab27b KO accelerates dopaminergic cell loss in the substantia nigra.","method":"Rab27b KO × A53T transgenic double mutant mice; AAV αsyn overexpression mouse model; proteinase-K resistance assay; phospho-αsyn immunohistochemistry; glia activation markers; nigral dopaminergic cell counting","journal":"bioRxiv : the preprint server for biology","confidence":"Medium","confidence_rationale":"Tier 2 — genetic KO in two independent in vivo PD models with mechanistic neuropathology readouts, preprint","pmids":["41509326"],"is_preprint":true},{"year":2025,"finding":"DDX10 physically interacts with Rab27b through phase separation and promotes Rab27b-mediated exosome secretion of PD-L1 in oral squamous cell carcinoma cells, contributing to T cell exhaustion.","method":"Co-immunoprecipitation of DDX10 and Rab27b; DDX10 knockdown; exosome PD-L1 quantification; T cell functional assays","journal":"Research (Washington, D.C.)","confidence":"Low","confidence_rationale":"Tier 3 — single Co-IP with functional readout, single lab, limited mechanistic depth on phase separation","pmids":["40352946"],"is_preprint":false},{"year":2025,"finding":"Rab27b in neurons is required for amyloid beta (Aβ) secretion via lysosomal exocytosis in hiPSC-derived neurons. Silencing Rab27b (or Munc13-4) significantly reduces lysosomal fusion events at the plasma membrane and blocks Aβ release into the extracellular space, as visualized by TIRF microscopy.","method":"TIRF microscopy of lysosome-plasma membrane fusion events in hiPSC-derived neurons; siRNA knockdown of Rab27b and Munc13-4; nanoscale flow cytometry of released particles","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 — direct TIRF visualization of lysosomal exocytosis events plus siRNA loss-of-function with quantitative Aβ secretion readout, preprint","pmids":["bio_10.1101_2025.03.01.640950"],"is_preprint":true}],"current_model":"RAB27B is a small GTPase that controls multiple regulated exocytic pathways by docking multivesicular endosomes and secretory/lysosomal granules at the plasma membrane; it acts through GTP/GDP cycling (with EPI64B as a specific GAP and MADD as a GEF), recruits effectors such as Slac2-c/MyRIP, Slp1, Slp3, and Munc13-4 to link granules to actin and microtubule motors, regulates NRAS palmitoylation via interaction with ZDHHC9 to control RAS membrane trafficking and signaling, and promotes lysosomal function and autophagic clearance of alpha-synuclein in neurons, with its transcription regulated by NF-E2, FOXO1, NRF2, β-catenin/Tcf-4, SMAD3, and CREB in a cell-type-specific manner."},"narrative":{"teleology":[{"year":2002,"claim":"Initial evidence placed RAB27B on secretory organelles and implicated its GTPase cycle in regulated secretion, establishing it as a functional paralog of RAB27A in endocrine cells and melanocytes.","evidence":"Dominant-negative Rab27b mutants inhibited ACTH secretion in pituitary AtT20 cells and redistributed melanosomes to the perinuclear region in melanocytes; Co-IP showed association with the effector granuphilin","pmids":["11956164","12060386"],"confidence":"High","gaps":["No loss-of-function genetic model yet","Effector repertoire largely unknown","Mechanism of membrane association unclear"]},{"year":2003,"claim":"RAB27B was shown to localize to multiple granule types in megakaryocytes and fusiform vesicles in urothelium, and its transcription was found to be NF-E2-dependent, revealing tissue-specific transcriptional control of the regulated secretory machinery.","evidence":"ChIP demonstrated NF-E2 occupancy at the Rab27b promoter in megakaryocytes; dominant-negative Rab27 impaired proplatelet formation; immuno-EM placed Rab27b on fusiform vesicles in bladder urothelium","pmids":["12907454","14625374"],"confidence":"High","gaps":["No Rab27b knockout mouse yet to confirm megakaryocyte phenotype in vivo","Functional role in urothelium inferred from localization, not direct loss-of-function"]},{"year":2004,"claim":"The identification of Slac2-c/MyRIP as a direct RAB27B effector on exocrine secretory granules established the paradigm of RAB27B recruiting linker proteins to couple granules to cytoskeletal motors for regulated exocytosis.","evidence":"Co-IP and immunohistochemistry in parotid acinar cells; functional blocking with recombinant SHD domain and antibodies inhibited amylase release; Rab27b GTP/GDP cycling mutants modulated pancreatic amylase secretion","pmids":["15039459","15451418"],"confidence":"High","gaps":["Identity of actin/microtubule motors downstream of Slac2-c not yet defined","Relative contributions of effectors in exocrine cells unknown"]},{"year":2007,"claim":"Genetic knockout studies in mice established RAB27B as essential for platelet dense granule biogenesis, mast cell degranulation, and polarized delivery of secretory granules to the plasma membrane in pituitary cells, confirming non-redundancy with RAB27A.","evidence":"Rab27b KO mice showed hemorrhagic disease, reduced dense granules, and impaired platelet aggregation; double KO pituitary cells lost polarized granule distribution; Rab27b KO mast cells showed impaired degranulation and increased microtubule-based granule movement","pmids":["17384153","17761531","17587407"],"confidence":"High","gaps":["Effector identity mediating platelet-specific vs. mast cell-specific functions not yet resolved","How Rab27b regulates granule number (biogenesis) vs. docking not mechanistically separated"]},{"year":2007,"claim":"The crystal structure of Rab27b-GDP revealed an unusually open switch region conformation with high flexibility, providing a structural basis for understanding its distinct effector recognition properties.","evidence":"X-ray crystallography in three crystal forms plus SAXS solution measurements of mouse Rab27b-GDP","pmids":["17582168"],"confidence":"High","gaps":["No structure of GTP-bound form","No co-crystal with any effector","Structural basis of Rab27a vs. Rab27b effector selectivity unresolved"]},{"year":2009,"claim":"RAB27B was shown to control multivesicular endosome docking at the plasma membrane for exosome secretion, expanding its role beyond classical secretory granule exocytosis to the exosome biogenesis pathway.","evidence":"RNAi screen in HeLa cells; Rab27b silencing redistributed MVEs to perinuclear region and reduced exosome secretion; effector Slac2-b phenocopied the knockdown","pmids":["19966785"],"confidence":"High","gaps":["MVE docking mechanism and fusion machinery downstream of Rab27b unknown","Whether Rab27b selects specific MVE cargo for exosomal release unclear"]},{"year":2010,"claim":"RAB27B was identified as an abundant synaptic vesicle protein that, unlike Rab3a, remains membrane-associated after exocytosis and resists GDI extraction, revealing a distinct recycling mechanism at presynaptic terminals.","evidence":"Quantitative iTRAQ proteomics and immunoblotting of purified synaptic vesicles; GDI extraction assay; manipulation of GTP/GDP switch impaired SV recycling","pmids":["20926670"],"confidence":"High","gaps":["Functional redundancy with Rab3a at the synapse not yet genetically dissected","Effectors mediating Rab27b function at the synapse not identified"]},{"year":2010,"claim":"RAB27B was found to promote breast cancer invasion by delivering HSP90α-containing vesicles whose secretion activates extracellular MMP-2, linking its vesicle trafficking function to tumor progression.","evidence":"GFP-RAB27B vesicle proteomics identified HSP90α cargo; siRNA, GTP-binding and geranylgeranylation mutants reduced invasion; orthotopic xenograft confirmed in vivo relevance","pmids":["20484105"],"confidence":"High","gaps":["How RAB27B vesicle cargo is selected unknown","Whether V-ATPase role is direct or indirect unclear"]},{"year":2013,"claim":"Genetic epistasis in mast cells resolved the division of labor between RAB27A and RAB27B: RAB27A/melanophilin/MyoVa controls cortical actin remodeling, while RAB27B/Munc13-4 directly mediates granule exocytosis, and EPI64B was identified as a RAB27B-specific GAP.","evidence":"Epistasis across ashen, Rab27b KO, double KO, leaden, dilute, and jinx mouse mast cells; EPI64B GAP activity shown by GTP-Rab27b pulldown with catalytic-dead mutagenesis in pancreatic acini","pmids":["23281710","23671284"],"confidence":"High","gaps":["Whether EPI64B is the sole GAP for Rab27b unknown","How Munc13-4 couples to SNARE-mediated fusion not resolved"]},{"year":2016,"claim":"The Kif5b/Slp3/Rab27b complex was defined as the PI3K-dependent machinery linking secretory granules to kinesin-1 for microtubule-based transport to the exocytic site, explaining how Rab27b coordinates the switch from microtubule to actin-based motility.","evidence":"Kif5b conditional KO mice; Co-IP of kinesin-1/Slp3/Rab27b; PI3K inhibitor disrupted complex assembly; passive systemic anaphylaxis and BMMC degranulation assays","pmids":["27810912"],"confidence":"High","gaps":["How PI3K signal triggers kinesin-1 recruitment to Slp3 mechanistically unclear","Whether this complex operates in cell types beyond mast cells untested"]},{"year":2020,"claim":"RAB27B was discovered to regulate autophagic clearance and lysosomal function in neurons, with its loss causing accumulation of insoluble alpha-synuclein and increased paracrine toxicity, and to be essential for hippocampal long-term potentiation.","evidence":"shRNA KD in neuronal α-syn model showed impaired LC3 turnover and increased insoluble α-syn; Rab27b KO mice completely lost MF-CA3 LTP, rescued by lentiviral human Rab27b re-expression","pmids":["32350025","32358861"],"confidence":"Medium","gaps":["Mechanistic link between Rab27b and autophagosome-lysosome fusion not established","Effector mediating LTP function unknown","Single-lab findings for each"]},{"year":2023,"claim":"RAB27B was shown to control NRAS palmitoylation and plasma membrane trafficking by interacting with the palmitoyl acyltransferase ZDHHC9, establishing a non-canonical function in RAS signaling regulation distinct from vesicle exocytosis.","evidence":"Co-IP of RAB27B and ZDHHC9; Rab27b KO mice with NRAS-mutant hematopoietic cells showed abrogated ERK signaling and reduced leukemia development; NRAS palmitoylation assays","pmids":["37317963"],"confidence":"High","gaps":["Whether RAB27B regulates palmitoylation of other substrates beyond NRAS unknown","Structural basis of RAB27B-ZDHHC9 interaction undefined","Whether this function is GTP-dependent not shown"]},{"year":2025,"claim":"Rab27b was established as essential for lysosomal enzyme maturation in neurons, with its genetic deletion causing lysosomal proteolytic defects and exacerbating alpha-synuclein aggregation and dopaminergic neurodegeneration in multiple in vivo Parkinson's disease models.","evidence":"Rab27b KO mouse neurons with lysosomal enzyme activity assays and pH measurements; A53T transgenic × Rab27b KO and AAV α-syn models showing increased PK-resistant α-syn and nigral cell loss; human PD/DLB brain tissue analysis","pmids":["39965930"],"confidence":"High","gaps":["Whether Rab27b loss is causally linked to human PD remains correlative","Specific lysosomal trafficking step regulated by Rab27b in neurons not defined","Effector mediating neuronal lysosomal function unknown"]},{"year":null,"claim":"Key unresolved questions include the structural basis of Rab27b effector selectivity versus Rab27a, the full effector code in each cell type, whether the ZDHHC9-mediated RAS palmitoylation function extends to other substrates, and whether Rab27b loss contributes causally to human neurodegenerative disease.","evidence":"","pmids":[],"confidence":"High","gaps":["No co-crystal structure of Rab27b with any effector","Comprehensive cell-type-specific effector mapping lacking","Causal link to human Parkinson's disease not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003924","term_label":"GTPase activity","supporting_discovery_ids":[6,14,17]}],"localization":[{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[0,2,6,8,10,24,25,27]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,9,25,27]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[23]},{"term_id":"GO:0005764","term_label":"lysosome","supporting_discovery_ids":[13,28,38,45]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,2,6,9,10,16,25,27]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[4,9,12]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[30,33]},{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[11,40]},{"term_id":"R-HSA-109582","term_label":"Hemostasis","supporting_discovery_ids":[1,7]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[29,38]}],"complexes":["Rab27b–Slac2-c/MyRIP","Rab27b–Munc13-4","Kif5b–Slp3–Rab27b","Rab27b–ZDHHC9"],"partners":["EXPH5","SYTL1","UNC13D","SYTL3","MYO5A","ZDHHC9","TBC1D10B","MADD"],"other_free_text":[]},"mechanistic_narrative":"RAB27B is a small GTPase that functions as a master regulator of regulated exocytosis, controlling the docking, maturation, and fusion of secretory granules, lysosome-related organelles, and multivesicular endosomes with the plasma membrane across a remarkably broad range of cell types including platelets, mast cells, neutrophils, exocrine acinar cells, parietal cells, neurons, melanocytes, and urothelial cells [PMID:17384153, PMID:19966785, PMID:15039459, PMID:20888820, PMID:29167152]. RAB27B cycles between GTP-bound active and GDP-bound inactive states regulated by the GAP EPI64B and the GEF MADD, and recruits effector proteins including Slac2-b/EXPH5, Slac2-c/MyRIP, Slp1, Slp3, and Munc13-4 that couple vesicles to actin- and microtubule-based motors for polarized transport to the exocytic site [PMID:23671284, PMID:37604243, PMID:15039459, PMID:27810912, PMID:23281710]. Beyond canonical secretion, RAB27B controls NRAS palmitoylation and plasma membrane trafficking through interaction with the palmitoyl acyltransferase ZDHHC9, thereby regulating RAS-ERK signaling in hematopoietic cells, and promotes lysosomal enzyme maturation and autophagic clearance of alpha-synuclein in neurons, with its loss exacerbating synucleinopathy and dopaminergic neurodegeneration in vivo [PMID:37317963, PMID:39965930, PMID:32350025]. RAB27B transcription is regulated in a cell-type-specific manner by NF-E2 in megakaryocytes, FOXO1 in kidney tubular cells, NRF2 in urothelium, β-catenin/Tcf-4 in colorectal cells, SMAD3 in breast cancer, and CREB downstream of ZIP4 in pancreatic cancer [PMID:12907454, PMID:33597203, PMID:34686330, PMID:30980673, PMID:39723610, PMID:30342032]."},"prefetch_data":{"uniprot":{"accession":"O00194","full_name":"Ras-related protein Rab-27B","aliases":["C25KG"],"length_aa":218,"mass_kda":24.6,"function":"The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:21775604, PubMed:30771381). RAB27B regulates homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion (PubMed:30771381). Plays a role in NTRK2/TRKB axonal anterograde transport by facilitating the association of NTRK2/TRKB with KLC1 (PubMed:21775604). May be involved in targeting uroplakins to urothelial apical membranes (By similarity)","subcellular_location":"Membrane; Late endosome","url":"https://www.uniprot.org/uniprotkb/O00194/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/RAB27B","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/RAB27B","total_profiled":1310},"omim":[{"mim_id":"615028","title":"EPIDERMOLYSIS BULLOSA SIMPLEX 4, LOCALIZED OR GENERALIZED INTERMEDIATE, AUTOSOMAL RECESSIVE; EBS4","url":"https://www.omim.org/entry/615028"},{"mim_id":"612878","title":"EXOPHILIN 5; EXPH5","url":"https://www.omim.org/entry/612878"},{"mim_id":"611790","title":"MYOSIN VIIA- AND RAB-INTERACTING PROTEIN; MYRIP","url":"https://www.omim.org/entry/611790"},{"mim_id":"608897","title":"UNC13 HOMOLOG D; UNC13D","url":"https://www.omim.org/entry/608897"},{"mim_id":"606526","title":"MELANOPHILIN; MLPH","url":"https://www.omim.org/entry/606526"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Golgi apparatus","reliability":"Approved"},{"location":"Plasma membrane","reliability":"Approved"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"stomach 1","ntpm":41.7}],"url":"https://www.proteinatlas.org/search/RAB27B"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"O00194","domains":[{"cath_id":"3.40.50.300","chopping":"9-190","consensus_level":"high","plddt":93.3061,"start":9,"end":190}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O00194","model_url":"https://alphafold.ebi.ac.uk/files/AF-O00194-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O00194-F1-predicted_aligned_error_v6.png","plddt_mean":84.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RAB27B","jax_strain_url":"https://www.jax.org/strain/search?query=RAB27B"},"sequence":{"accession":"O00194","fasta_url":"https://rest.uniprot.org/uniprotkb/O00194.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O00194/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O00194"}},"corpus_meta":[{"pmid":"19966785","id":"PMC_19966785","title":"Rab27a and Rab27b control different steps of the exosome secretion pathway.","date":"2009","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/19966785","citation_count":2134,"is_preprint":false},{"pmid":"20484105","id":"PMC_20484105","title":"Effect of the secretory small GTPase Rab27B on breast cancer growth, invasion, and metastasis.","date":"2010","source":"Journal of the National Cancer Institute","url":"https://pubmed.ncbi.nlm.nih.gov/20484105","citation_count":198,"is_preprint":false},{"pmid":"17384153","id":"PMC_17384153","title":"Rab27b regulates number and secretion of platelet dense granules.","date":"2007","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/17384153","citation_count":151,"is_preprint":false},{"pmid":"30342032","id":"PMC_30342032","title":"ZIP4 Promotes Muscle Wasting and Cachexia in Mice With Orthotopic Pancreatic Tumors by Stimulating RAB27B-Regulated Release of Extracellular Vesicles From Cancer Cells.","date":"2018","source":"Gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/30342032","citation_count":120,"is_preprint":false},{"pmid":"30980673","id":"PMC_30980673","title":"RAB27B-activated secretion of stem-like tumor exosomes delivers the biomarker microRNA-146a-5p, which promotes tumorigenesis and associates with an immunosuppressive tumor microenvironment in colorectal cancer.","date":"2019","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/30980673","citation_count":109,"is_preprint":false},{"pmid":"9066979","id":"PMC_9066979","title":"Molecular cloning and characterization of rab27a and rab27b, novel human rab proteins shared by melanocytes and platelets.","date":"1997","source":"Biochemical and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/9066979","citation_count":105,"is_preprint":false},{"pmid":"29479064","id":"PMC_29479064","title":"miR-34c-5p promotes eradication of acute myeloid leukemia stem cells by inducing senescence through selective RAB27B targeting to inhibit exosome shedding.","date":"2018","source":"Leukemia","url":"https://pubmed.ncbi.nlm.nih.gov/29479064","citation_count":95,"is_preprint":false},{"pmid":"15039459","id":"PMC_15039459","title":"The small GTPase Rab27B regulates amylase release from rat parotid acinar cells.","date":"2004","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/15039459","citation_count":94,"is_preprint":false},{"pmid":"17761531","id":"PMC_17761531","title":"Rab27b is expressed in a wide range of exocytic cells and involved in the delivery of secretory granules near the plasma membrane.","date":"2007","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/17761531","citation_count":92,"is_preprint":false},{"pmid":"17587407","id":"PMC_17587407","title":"Rab27b regulates mast cell granule dynamics and secretion.","date":"2007","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/17587407","citation_count":91,"is_preprint":false},{"pmid":"20028487","id":"PMC_20028487","title":"Rab27a and Rab27b regulate neutrophil azurophilic granule exocytosis and NADPH oxidase activity by independent mechanisms.","date":"2009","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/20028487","citation_count":88,"is_preprint":false},{"pmid":"26913720","id":"PMC_26913720","title":"MiR-193a-3p and miR-193a-5p suppress the metastasis of human osteosarcoma cells by down-regulating Rab27B and SRR, respectively.","date":"2016","source":"Clinical & experimental metastasis","url":"https://pubmed.ncbi.nlm.nih.gov/26913720","citation_count":87,"is_preprint":false},{"pmid":"20926670","id":"PMC_20926670","title":"Quantitative analysis of synaptic vesicle Rabs uncovers distinct yet overlapping roles for Rab3a and Rab27b in Ca2+-triggered exocytosis.","date":"2010","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/20926670","citation_count":86,"is_preprint":false},{"pmid":"11956164","id":"PMC_11956164","title":"Involvement of Rab27b in the regulated secretion of pituitary hormones.","date":"2002","source":"Endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/11956164","citation_count":82,"is_preprint":false},{"pmid":"12907454","id":"PMC_12907454","title":"A role for Rab27b in NF-E2-dependent pathways of platelet formation.","date":"2003","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/12907454","citation_count":77,"is_preprint":false},{"pmid":"26348397","id":"PMC_26348397","title":"Rab7a and Rab27b control secretion of endothelial microRNA through extracellular vesicles.","date":"2015","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/26348397","citation_count":69,"is_preprint":false},{"pmid":"14625374","id":"PMC_14625374","title":"Rab27b is associated with fusiform vesicles and may be involved in targeting uroplakins to urothelial apical membranes.","date":"2003","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/14625374","citation_count":69,"is_preprint":false},{"pmid":"33317598","id":"PMC_33317598","title":"Human multipotent mesenchymal stromal cells cytokine priming promotes RAB27B-regulated secretion of small extracellular vesicles with immunomodulatory cargo.","date":"2020","source":"Stem cell research & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/33317598","citation_count":62,"is_preprint":false},{"pmid":"23281710","id":"PMC_23281710","title":"Distinct and opposing roles for Rab27a/Mlph/MyoVa and Rab27b/Munc13-4 in mast cell secretion.","date":"2013","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/23281710","citation_count":62,"is_preprint":false},{"pmid":"15451418","id":"PMC_15451418","title":"Rab27b localizes to zymogen granules and regulates pancreatic acinar exocytosis.","date":"2004","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/15451418","citation_count":59,"is_preprint":false},{"pmid":"23176819","id":"PMC_23176819","title":"Germline Mutation in EXPH5 Implicates the Rab27B Effector Protein Slac2-b in Inherited Skin Fragility.","date":"2012","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/23176819","citation_count":57,"is_preprint":false},{"pmid":"11178108","id":"PMC_11178108","title":"Chromosomal mapping, gene structure and characterization of the human and murine RAB27B gene.","date":"2001","source":"BMC genetics","url":"https://pubmed.ncbi.nlm.nih.gov/11178108","citation_count":50,"is_preprint":false},{"pmid":"23390068","id":"PMC_23390068","title":"Vacuolar H+ ATPase expression and activity is required for Rab27B-dependent invasive growth and metastasis of breast cancer.","date":"2013","source":"International journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/23390068","citation_count":48,"is_preprint":false},{"pmid":"18478159","id":"PMC_18478159","title":"Intramanchette transport during primate spermiogenesis: expression of dynein, myosin Va, motor recruiter myosin Va, VIIa-Rab27a/b interacting protein, and Rab27b in the manchette during human and monkey spermiogenesis.","date":"2008","source":"Asian journal of andrology","url":"https://pubmed.ncbi.nlm.nih.gov/18478159","citation_count":47,"is_preprint":false},{"pmid":"37317963","id":"PMC_37317963","title":"RAB27B controls palmitoylation-dependent NRAS trafficking and signaling in myeloid leukemia.","date":"2023","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/37317963","citation_count":41,"is_preprint":false},{"pmid":"21304180","id":"PMC_21304180","title":"The secretory small GTPase Rab27B as a marker for breast cancer progression.","date":"2010","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/21304180","citation_count":39,"is_preprint":false},{"pmid":"15357836","id":"PMC_15357836","title":"Rab27b is up-regulated in human Griscelli syndrome type II melanocytes and linked to the actin cytoskeleton via exon F-Myosin Va transcripts.","date":"2004","source":"Pigment cell research","url":"https://pubmed.ncbi.nlm.nih.gov/15357836","citation_count":39,"is_preprint":false},{"pmid":"34686330","id":"PMC_34686330","title":"NRF2 promotes urothelial cell response to bacterial infection by regulating reactive oxygen species and RAB27B expression.","date":"2021","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/34686330","citation_count":38,"is_preprint":false},{"pmid":"27810912","id":"PMC_27810912","title":"Kinesin-1 controls mast cell degranulation and anaphylaxis through PI3K-dependent recruitment to the granular Slp3/Rab27b complex.","date":"2016","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/27810912","citation_count":37,"is_preprint":false},{"pmid":"28265202","id":"PMC_28265202","title":"MiR-20a-5p promotes radio-resistance by targeting Rab27B in nasopharyngeal cancer cells.","date":"2017","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/28265202","citation_count":36,"is_preprint":false},{"pmid":"28902788","id":"PMC_28902788","title":"Effects of Rab27A and Rab27B on Invasion, Proliferation, Apoptosis, and Chemoresistance in Human Pancreatic Cancer Cells.","date":"2017","source":"Pancreas","url":"https://pubmed.ncbi.nlm.nih.gov/28902788","citation_count":34,"is_preprint":false},{"pmid":"32379831","id":"PMC_32379831","title":"Oncogenic effects of RAB27B through exosome independent function in renal cell carcinoma including sunitinib-resistant.","date":"2020","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/32379831","citation_count":32,"is_preprint":false},{"pmid":"32350025","id":"PMC_32350025","title":"The GTPase Rab27b regulates the release, autophagic clearance, and toxicity of α-synuclein.","date":"2020","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/32350025","citation_count":31,"is_preprint":false},{"pmid":"28197629","id":"PMC_28197629","title":"RAB27A, RAB27B and VPS36 are downregulated in advanced prostate cancer and show functional relevance in prostate cancer cells.","date":"2017","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/28197629","citation_count":30,"is_preprint":false},{"pmid":"20939018","id":"PMC_20939018","title":"Rab27a and Rab27b are involved in stimulation-dependent RANKL release from secretory lysosomes in osteoblastic cells.","date":"2011","source":"Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research","url":"https://pubmed.ncbi.nlm.nih.gov/20939018","citation_count":30,"is_preprint":false},{"pmid":"12060386","id":"PMC_12060386","title":"Rab27b association with melanosomes: dominant negative mutants disrupt melanosomal movement.","date":"2002","source":"The Journal of investigative dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/12060386","citation_count":29,"is_preprint":false},{"pmid":"32390047","id":"PMC_32390047","title":"Rab27B enhances drug resistance in hepatocellular carcinoma by promoting exosome-mediated drug efflux.","date":"2020","source":"Carcinogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/32390047","citation_count":27,"is_preprint":false},{"pmid":"21525430","id":"PMC_21525430","title":"Rab27b regulates exocytosis of secretory vesicles in acinar epithelial cells from the lacrimal gland.","date":"2011","source":"American journal of physiology. Cell physiology","url":"https://pubmed.ncbi.nlm.nih.gov/21525430","citation_count":27,"is_preprint":false},{"pmid":"32737155","id":"PMC_32737155","title":"Androgen Receptor Signaling Reduces the Efficacy of Bacillus Calmette-Guérin Therapy for Bladder Cancer via Modulating Rab27b-Induced Exocytosis.","date":"2020","source":"Molecular cancer therapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/32737155","citation_count":26,"is_preprint":false},{"pmid":"27325508","id":"PMC_27325508","title":"Rab27b is Involved in Lysosomal Exocytosis and Proteolipid Protein Trafficking in Oligodendrocytes.","date":"2016","source":"Neuroscience bulletin","url":"https://pubmed.ncbi.nlm.nih.gov/27325508","citation_count":25,"is_preprint":false},{"pmid":"31002890","id":"PMC_31002890","title":"Inactivation of Rab27B-dependent signaling pathway by calycosin inhibits migration and invasion of ER-negative breast cancer cells.","date":"2019","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/31002890","citation_count":23,"is_preprint":false},{"pmid":"33597203","id":"PMC_33597203","title":"FOXO1-Mediated Downregulation of RAB27B Leads to Decreased Exosome Secretion in Diabetic Kidneys.","date":"2021","source":"Diabetes","url":"https://pubmed.ncbi.nlm.nih.gov/33597203","citation_count":22,"is_preprint":false},{"pmid":"29963197","id":"PMC_29963197","title":"MicroRNA-599 suppresses glioma progression by targeting RAB27B.","date":"2018","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/29963197","citation_count":22,"is_preprint":false},{"pmid":"17582168","id":"PMC_17582168","title":"Structure of the small GTPase Rab27b shows an unexpected swapped dimer.","date":"2007","source":"Acta crystallographica. Section D, Biological crystallography","url":"https://pubmed.ncbi.nlm.nih.gov/17582168","citation_count":22,"is_preprint":false},{"pmid":"16620919","id":"PMC_16620919","title":"Expression of RAB27B is up-regulated in senescent human cells.","date":"2006","source":"Mechanisms of ageing and development","url":"https://pubmed.ncbi.nlm.nih.gov/16620919","citation_count":20,"is_preprint":false},{"pmid":"19583748","id":"PMC_19583748","title":"Redistribution of small GTP-binding protein, Rab27B, in rat parotid acinar cells after stimulation with isoproterenol.","date":"2009","source":"European journal of oral sciences","url":"https://pubmed.ncbi.nlm.nih.gov/19583748","citation_count":19,"is_preprint":false},{"pmid":"36581340","id":"PMC_36581340","title":"Rab27b, a Regulator of Exosome Secretion, Is Associated With Peritoneal Metastases in Gastric Cancer.","date":"2023","source":"Cancer genomics & proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/36581340","citation_count":19,"is_preprint":false},{"pmid":"38036630","id":"PMC_38036630","title":"RAB27B-regulated exosomes mediate LSC maintenance via resistance to senescence and crosstalk with the microenvironment.","date":"2023","source":"Leukemia","url":"https://pubmed.ncbi.nlm.nih.gov/38036630","citation_count":18,"is_preprint":false},{"pmid":"18477466","id":"PMC_18477466","title":"Expression of Rab27B-binding protein Slp1 in pancreatic acinar cells and its involvement in amylase secretion.","date":"2008","source":"Archives of biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/18477466","citation_count":18,"is_preprint":false},{"pmid":"29167152","id":"PMC_29167152","title":"RAB27B requirement for stretch-induced exocytosis in bladder umbrella cells.","date":"2017","source":"American journal of physiology. Cell physiology","url":"https://pubmed.ncbi.nlm.nih.gov/29167152","citation_count":17,"is_preprint":false},{"pmid":"23671284","id":"PMC_23671284","title":"EPI64B acts as a GTPase-activating protein for Rab27B in pancreatic acinar cells.","date":"2013","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/23671284","citation_count":15,"is_preprint":false},{"pmid":"32351955","id":"PMC_32351955","title":"The Small GTPases Rab27b Regulates Mitochondrial Fatty Acid Oxidative Metabolism of Cardiac Mesenchymal Stem Cells.","date":"2020","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/32351955","citation_count":15,"is_preprint":false},{"pmid":"29096746","id":"PMC_29096746","title":"Overexpression of microRNA-133b reduces myocardial injuries in children with viral myocarditis by targeting Rab27B gene.","date":"2017","source":"Cellular and molecular biology (Noisy-le-Grand, France)","url":"https://pubmed.ncbi.nlm.nih.gov/29096746","citation_count":14,"is_preprint":false},{"pmid":"33845096","id":"PMC_33845096","title":"The calcium sensing receptor (CaSR) promotes Rab27B expression and activity to control secretion in breast cancer cells.","date":"2021","source":"Biochimica et biophysica acta. Molecular cell research","url":"https://pubmed.ncbi.nlm.nih.gov/33845096","citation_count":14,"is_preprint":false},{"pmid":"20888820","id":"PMC_20888820","title":"Rab27b localizes to the tubulovesicle membranes of gastric parietal cells and regulates acid secretion.","date":"2010","source":"Gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/20888820","citation_count":13,"is_preprint":false},{"pmid":"35985682","id":"PMC_35985682","title":"RAB27A and RAB27B Expression May Predict Lymph Node Metastasis and Survival in Patients With Gastric Cancer.","date":"2022","source":"Cancer genomics & proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/35985682","citation_count":13,"is_preprint":false},{"pmid":"37692484","id":"PMC_37692484","title":"The m6A regulator KIAA1429 stabilizes RAB27B mRNA and promotes the progression of chronic myeloid leukemia and resistance to targeted therapy.","date":"2023","source":"Genes & diseases","url":"https://pubmed.ncbi.nlm.nih.gov/37692484","citation_count":11,"is_preprint":false},{"pmid":"34594410","id":"PMC_34594410","title":"Silencing of long non-coding RNA SNHG15 suppresses proliferation, migration and invasion of pancreatic cancer cells by regulating the microRNA-345-5p/RAB27B axis.","date":"2021","source":"Experimental and therapeutic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/34594410","citation_count":10,"is_preprint":false},{"pmid":"32358861","id":"PMC_32358861","title":"Actions of Rab27B-GTPase on mammalian central excitatory synaptic transmission.","date":"2020","source":"Physiological reports","url":"https://pubmed.ncbi.nlm.nih.gov/32358861","citation_count":9,"is_preprint":false},{"pmid":"37077938","id":"PMC_37077938","title":"RAB27B Drives a Cancer Stem Cell Phenotype in NSCLC Cells Through Enhanced Extracellular Vesicle Secretion.","date":"2023","source":"Cancer research communications","url":"https://pubmed.ncbi.nlm.nih.gov/37077938","citation_count":9,"is_preprint":false},{"pmid":"37139869","id":"PMC_37139869","title":"Atorvastatin-mediated inhibition of prenylation of Rab27b and Rap1a in platelets attenuates their prothrombotic capacity and modulates clot structure.","date":"2023","source":"Platelets","url":"https://pubmed.ncbi.nlm.nih.gov/37139869","citation_count":9,"is_preprint":false},{"pmid":"35164665","id":"PMC_35164665","title":"RAB27B inhibits proliferation and promotes apoptosis of leukemic cells via 3-Hydroxy butyrate dehydrogenase 2 (BDH2).","date":"2022","source":"Bioengineered","url":"https://pubmed.ncbi.nlm.nih.gov/35164665","citation_count":8,"is_preprint":false},{"pmid":"33409495","id":"PMC_33409495","title":"Rab27b contributes to radioresistance and exerts a paracrine effect via epiregulin in glioblastoma.","date":"2020","source":"Neuro-oncology advances","url":"https://pubmed.ncbi.nlm.nih.gov/33409495","citation_count":8,"is_preprint":false},{"pmid":"22363735","id":"PMC_22363735","title":"Direct imaging of RAB27B-enriched secretory vesicle biogenesis in lacrimal acinar cells reveals origins on a nascent vesicle budding site.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22363735","citation_count":8,"is_preprint":false},{"pmid":"32784729","id":"PMC_32784729","title":"Inhibition of Rab27a and Rab27b Has Opposite Effects on the Regulation of Hair Cycle and Hair Growth.","date":"2020","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/32784729","citation_count":7,"is_preprint":false},{"pmid":"22811270","id":"PMC_22811270","title":"An immunohistochemical analysis of Rab27B distribution in fetal and adult tissue.","date":"2012","source":"The International journal of developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/22811270","citation_count":7,"is_preprint":false},{"pmid":"37641372","id":"PMC_37641372","title":"Rab27b promotes endometriosis by enhancing invasiveness of ESCs and promoting angiogenesis.","date":"2023","source":"American journal of reproductive immunology (New York, N.Y. : 1989)","url":"https://pubmed.ncbi.nlm.nih.gov/37641372","citation_count":6,"is_preprint":false},{"pmid":"22349512","id":"PMC_22349512","title":"Rab27b regulates c-kit expression by controlling the secretion of stem cell factor.","date":"2012","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/22349512","citation_count":6,"is_preprint":false},{"pmid":"33877577","id":"PMC_33877577","title":"Rab27b regulates extracellular vesicle production in cells infected with Kaposi's sarcoma-associated herpesvirus to promote cell survival and persistent infection.","date":"2021","source":"Journal of microbiology (Seoul, Korea)","url":"https://pubmed.ncbi.nlm.nih.gov/33877577","citation_count":6,"is_preprint":false},{"pmid":"26845357","id":"PMC_26845357","title":"Genetic deletion of Rab27B in pancreatic acinar cells affects granules size and has inhibitory effects on amylase secretion.","date":"2016","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/26845357","citation_count":6,"is_preprint":false},{"pmid":"39723610","id":"PMC_39723610","title":"TGF-β regulates the release of breast cancer cell-derived extracellular vesicles and the sorting of their protein cargo by downregulating RAB27B expression.","date":"2024","source":"Journal of extracellular vesicles","url":"https://pubmed.ncbi.nlm.nih.gov/39723610","citation_count":5,"is_preprint":false},{"pmid":"39965930","id":"PMC_39965930","title":"Rab27b Promotes Lysosomal Function and Alpha-Synuclein Clearance in Neurons.","date":"2025","source":"The Journal of neuroscience : the official journal of the Society for Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/39965930","citation_count":4,"is_preprint":false},{"pmid":"37604243","id":"PMC_37604243","title":"CaSR links endocytic and secretory pathways via MADD, a Rab11A effector that activates Rab27B.","date":"2023","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/37604243","citation_count":4,"is_preprint":false},{"pmid":"39542128","id":"PMC_39542128","title":"Regulation of autophagy by Rab27B in colorectal cancer.","date":"2024","source":"The international journal of biochemistry & cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/39542128","citation_count":3,"is_preprint":false},{"pmid":"38441297","id":"PMC_38441297","title":"Tectoridin inhibits the growth of bladder cancer by regulating PI3K/MAPK pathway through RAB27B.","date":"2024","source":"Molecular carcinogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/38441297","citation_count":3,"is_preprint":false},{"pmid":"40352946","id":"PMC_40352946","title":"DDX10 Exacerbates Exosomal PD-L1-Dependent T Cell Exhaustion via Phase Separation of Rab27b in Oral Squamous Cell Carcinoma.","date":"2025","source":"Research (Washington, D.C.)","url":"https://pubmed.ncbi.nlm.nih.gov/40352946","citation_count":2,"is_preprint":false},{"pmid":"33285290","id":"PMC_33285290","title":"Abnormal expression of Rab27B in prostatic epithelial cells of benign prostatic hyperplasia alters intercellular communication.","date":"2020","source":"The international journal of biochemistry & cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/33285290","citation_count":2,"is_preprint":false},{"pmid":"40972800","id":"PMC_40972800","title":"Rab27b-mediated CAFs derived exosomal miR-22-3p suppresses ferroptosis and promotes cisplatin resistance in osteosarcoma.","date":"2025","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/40972800","citation_count":2,"is_preprint":false},{"pmid":"40399992","id":"PMC_40399992","title":"Mechanism of LINC01018/miR-182-5p/Rab27B in the immune escape through PD-L1-mediated CD8+ T cell suppression in glioma.","date":"2025","source":"Biology direct","url":"https://pubmed.ncbi.nlm.nih.gov/40399992","citation_count":1,"is_preprint":false},{"pmid":"41163097","id":"PMC_41163097","title":"Microgravity-driven Rab27B activation amplifies mesenchymal stem cell-derived extracellular vesicle production and functions.","date":"2025","source":"Stem cell research & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/41163097","citation_count":1,"is_preprint":false},{"pmid":"38979346","id":"PMC_38979346","title":"Rab27b promotes lysosomal function and alpha-synuclein clearance in neurons.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/38979346","citation_count":1,"is_preprint":false},{"pmid":"40441460","id":"PMC_40441460","title":"Lichong Decoction represses colorectal cancer progression via inhibiting the PINK1/Parkin pathway regulated by Rab27B.","date":"2025","source":"Journal of ethnopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/40441460","citation_count":0,"is_preprint":false},{"pmid":"41509326","id":"PMC_41509326","title":"Knockout of Rab27b exacerbates neuropathology in alpha-synuclein mouse models.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/41509326","citation_count":0,"is_preprint":false},{"pmid":"39899936","id":"PMC_39899936","title":"Positive feedback loop between NRASQ61R mutation and RAB27B expression in endothelial cells.","date":"2025","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/39899936","citation_count":0,"is_preprint":false},{"pmid":"40692767","id":"PMC_40692767","title":"[Retracted] Silencing of long non-coding RNA SNHG15 suppresses proliferation, migration and invasion of pancreatic cancer cells by regulating the microRNA-345-5p/RAB27B axis.","date":"2025","source":"Experimental and therapeutic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/40692767","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.03.01.640950","title":"Amyloid beta is released by lysosomal exocytosis from hiPSC-derived neurons","date":"2025-03-06","source":"bioRxiv","url":"https://doi.org/10.1101/2025.03.01.640950","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.12.12.628185","title":"Phthalates Impair Estrogenic Regulation of HIF2α and Extracellular Vesicle Secretion by Human Endometrial Stromal Cells","date":"2024-12-17","source":"bioRxiv","url":"https://doi.org/10.1101/2024.12.12.628185","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.07.09.663949","title":"Human Decidual RUNX1 Promotes Angiogenesis and Trophoblast Differentiation by Regulating Extracellular Vesicle Signaling","date":"2025-07-14","source":"bioRxiv","url":"https://doi.org/10.1101/2025.07.09.663949","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":44604,"output_tokens":11853,"usd":0.155804},"stage2":{"model":"claude-opus-4-6","input_tokens":15914,"output_tokens":4159,"usd":0.275317},"total_usd":0.431121,"stage1_batch_id":"msgbatch_01SUR8NDzVrNmyszWyJeCct7","stage2_batch_id":"msgbatch_01G7Yfutko3cDWzejrwH5AMx","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2009,\n      \"finding\": \"RAB27B controls MVE (multivesicular endosome) docking at the plasma membrane; Rab27b silencing redistributes MVEs toward the perinuclear region, distinct from Rab27a which controls MVE size. The Rab27b effector Slac2b (EXPH5) phenocopies Rab27b silencing and inhibits exosome secretion.\",\n      \"method\": \"RNAi screen in HeLa cells; siRNA silencing; fluorescence microscopy of MVE localization; exosome quantification\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — systematic RNAi screen with multiple orthogonal readouts, replicated with effector knockdown, highly cited foundational study\",\n      \"pmids\": [\"19966785\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Rab27b is required for regulated secretion and correct number of platelet dense granules; Rab27b KO mice exhibit hemorrhagic disease, impaired platelet aggregation, reduced dense granule secretion, and ~50% reduction in dense granule number per platelet. Rab27a partially compensates for the secretory defect but not the reduced granule number.\",\n      \"method\": \"Rab27b knockout mouse generation; crossed with Rab27a ashen KO to produce double KO; in vitro platelet aggregation assays; dense granule secretion assays; electron microscopy\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic KO mouse with multiple orthogonal functional readouts, replicated in double KO\",\n      \"pmids\": [\"17384153\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Rab27B localizes to amylase-containing secretory granules in rat parotid acinar cells and forms a complex with the effector Slac2-c/MyRIP on secretory granules in vivo. Disruption of the Rab27B–Slac2-c complex (by recombinant Slp homology domain or blocking antibodies) strongly inhibits isoproterenol-stimulated amylase release.\",\n      \"method\": \"Subcellular fractionation; immunoprecipitation; immunohistochemistry; functional blocking with recombinant protein and antibodies in streptolysin O-permeabilized cells\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods including Co-IP, localization, and functional inhibition assay with mechanistic specificity\",\n      \"pmids\": [\"15039459\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Rab27b is expressed in a wide range of exocytic cells and is involved in delivering secretory granules near the plasma membrane (the exocytic site). In pituitary double Rab27a/Rab27b KO mice, polarized distribution of secretory granules close to the plasma membrane is markedly impaired.\",\n      \"method\": \"LacZ knock-in reporter mouse for expression analysis; Rab27a/Rab27b double knockout mice generated by crossing; electron microscopy of secretory granule distribution in pituitary cells\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic double KO model with direct ultrastructural readout of granule positioning\",\n      \"pmids\": [\"17761531\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Rab27b localizes to secretory granules in mast cells and is required for mast cell degranulation (beta-hexosaminidase release) and passive cutaneous anaphylaxis in vivo. Rab27b-deficient BMMC show ~10-fold increase in granules with fast microtubule-based movement, suggesting Rab27b regulates the transition from microtubule to actin-based granule motility.\",\n      \"method\": \"Rab27b KO and double KO mice; bone marrow-derived mast cell (BMMC) cultures; beta-hexosaminidase release assays; passive cutaneous anaphylaxis in vivo; live-cell time-lapse imaging; nocodazole treatment\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic KO with in vitro and in vivo functional readouts plus live-cell imaging mechanistic insight\",\n      \"pmids\": [\"17587407\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Rab27b associates with secretory granules and the effector granuphilin in pituitary endocrine cells (AtT20). Overexpression of inactive mutant Rab27b N133I significantly inhibits basal and forskolin-induced ACTH secretion.\",\n      \"method\": \"Subcellular fractionation; co-immunoprecipitation with granuphilin; dominant-negative overexpression; ACTH secretion assay\",\n      \"journal\": \"Endocrinology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP plus dominant-negative functional assay with specific secretion readout\",\n      \"pmids\": [\"11956164\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Rab27b localizes to zymogen granule membranes in pancreatic acinar cells. Constitutively active Rab27b Q78L enhances CCK-induced amylase release by ~92%, while dominant-negative Rab27b N133I inhibits release by ~53%, demonstrating a role for Rab27b GTP/GDP cycling in pancreatic acinar exocytosis.\",\n      \"method\": \"Proteomics (MALDI-MS/MS) identification; Western blot and immunocytochemistry for localization; adenoviral overexpression of WT, Q78L, and N133I mutants; amylase secretion assay\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — proteomic identification plus gain/loss-of-function mutagenesis with quantitative functional readout\",\n      \"pmids\": [\"15451418\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Rab27b localizes to alpha and dense granules in megakaryocytes. Inhibition of endogenous Rab27 function in primary megakaryocytes causes severe quantitative and qualitative defects in proplatelet formation. NF-E2 transcription factor is recruited to the Rab27B promoter and is required for its expression during terminal megakaryocyte differentiation.\",\n      \"method\": \"Immunofluorescence localization; dominant-negative Rab27 inhibition in primary megakaryocytes; chromatin immunoprecipitation (ChIP) for NF-E2 at Rab27B promoter; analysis of gunmetal mice\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — ChIP demonstrating transcriptional regulation plus dominant-negative functional assay in primary cells\",\n      \"pmids\": [\"12907454\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Rab27b associates with the cytoplasmic face of fusiform vesicles in bladder urothelial umbrella cells and its expression is differentiation-dependent, suggesting a role in targeting uroplakins to the apical plasma membrane.\",\n      \"method\": \"Immuno-electron microscopy; Western blot comparing urothelial tissue vs. cultured cells; differentiation-dependent expression analysis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct immuno-EM localization to specific vesicle type, but functional consequence inferred from correlative data\",\n      \"pmids\": [\"14625374\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Rab27a and Rab27b both regulate azurophilic granule exocytosis and NADPH oxidase recruitment to the plasma membrane in neutrophils via independent mechanisms. TIRF microscopy shows both isoforms are required for granule docking near the plasma membrane; upregulation of Rab27b in Rab27a-deficient cells does not compensate for the Rab27a secretory defect.\",\n      \"method\": \"Rab27a(ash/ash), Rab27b KO, and double KO mouse neutrophils; azurophilic granule exocytosis assays; TIRF microscopy of granule proximity to plasma membrane; NADPH oxidase activity assay\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic KO models with multiple orthogonal functional assays and direct imaging\",\n      \"pmids\": [\"20028487\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"RAB27B promotes invasive growth of ER-positive breast cancer cells through GTP- and geranylgeranyl-dependent delivery of secretory vesicles. Mass spectrometry of RAB27B-positive vesicles identified HSP90α as a key cargo; RAB27B-dependent HSP90α secretion is required for MMP-2 activation and invasion.\",\n      \"method\": \"GFP-RAB27B overexpression; point mutants defective in GTP binding or geranylgeranylation; siRNA silencing; Matrigel and collagen invasion assays; mass spectrometry of purified RAB27B vesicles; orthotopic xenograft mouse model\",\n      \"journal\": \"Journal of the National Cancer Institute\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods including proteomics, mutagenesis, in vitro invasion, and in vivo xenograft with mechanistic follow-up\",\n      \"pmids\": [\"20484105\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Rab27b is an abundant synaptic vesicle Rab GTPase that, unlike Rab3a, persists on synaptic vesicle membranes upon Ca2+-triggered exocytosis and is resistant to GDI-mediated retrieval. Modulation of the Rab27b GTP/GDP switch impairs synaptic vesicle recycling.\",\n      \"method\": \"Quantitative mass spectrometry (iTRAQ) of synaptic vesicles; quantitative immunoblotting; fluorescence microscopy; GDI extraction assay; Rab27b GTP/GDP switch manipulation\",\n      \"journal\": \"The Journal of neuroscience : the official journal of the Society for Neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — quantitative proteomics plus mechanistic GTP/GDP switch manipulation with functional readout\",\n      \"pmids\": [\"20926670\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"In mast cells, Rab27a and Rab27b regulate distinct steps of degranulation: Rab27a/Mlph/MyoVa regulates cortical actin stability upstream of granule exocytosis, while Rab27b/Munc13-4 directly mediates granule exocytosis. Munc13-4-deficient mast cells phenocopy the Rab27b KO secretory impairment.\",\n      \"method\": \"Bone marrow-derived mast cells from multiple mutant mouse lines (ashen Rab27a, Rab27b KO, double KO, leaden Mlph KO, dilute MyoVa KO, jinx Munc13-4 KO); beta-hexosaminidase release assays; F-actin immunofluorescence; epistasis analysis\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis across multiple mutant lines with mechanistic pathway placement\",\n      \"pmids\": [\"23281710\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Rab27b regulates stimulation-dependent RANKL release from secretory lysosomes in osteoblastic cells. Suppression of Rab27b inhibits fusion of RANKL-containing lysosomal vesicles with the plasma membrane. The effectors Slp4-a, Slp5, and Munc13-4 coordinate Rab27a/b activity in this pathway; Munc13-4-deficient (jinx) mice show increased bone volume due to reduced osteoclast activity.\",\n      \"method\": \"siRNA knockdown of Rab27a, Rab27b, Slp4-a, Slp5, Munc13-4 in osteoblastic cells; RANKL release assays; immunofluorescence of vesicle localization; jinx mouse bone phenotype analysis\",\n      \"journal\": \"Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — RNAi epistasis with effector proteins plus in vivo genetic model with bone phenotype readout\",\n      \"pmids\": [\"20939018\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Crystal structure of mouse Rab27b-GDP reveals an open conformation with protruding switch and interswitch regions, stabilized through domain-swapping dimerization in the crystal. SAXS measurements show an extended monomer in solution, indicating highly flexible switch regions relevant to effector interaction.\",\n      \"method\": \"X-ray crystallography in three distinct crystal lattices; small-angle X-ray scattering (SAXS)\",\n      \"journal\": \"Acta crystallographica. Section D, Biological crystallography\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure determination with solution validation by SAXS\",\n      \"pmids\": [\"17582168\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"The Rab27b effector Slac2-b (EXPH5) colocalizes with Rab27b and β4 integrin at early adhesion initiation sites in spreading keratinocytes. Loss-of-function of Slac2-b (frameshift mutation in humans or shRNA knockdown) causes keratinocyte adhesion disruption, cytoskeletal disruption, and increased perinuclear vesicles, establishing a role for the Rab27B–Slac2-b complex in keratinocyte biology.\",\n      \"method\": \"Whole-exome sequencing of human patients; immunofluorescence co-localization; shRNA knockdown in normal keratinocytes; cell adhesion assays\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — human loss-of-function mutation validated by shRNA model with orthogonal functional and localization readouts\",\n      \"pmids\": [\"23176819\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Rab27b is required for exocytosis of secretory vesicles in lacrimal gland acinar cells. Constitutively active Rab27b increases the average size of secretory vesicles while retaining subapical distribution; dominant-negative Rab27b redistributes Rab27b to cytoplasm. Rab27b KO and double KO mice (but not Rab27a ashen mice) show changes in abundance and organization of secretory vesicles. Disruption of actin filaments inhibits vesicle fusion to the apical membrane but not homotypic fusion.\",\n      \"method\": \"Confocal fluorescence microscopy; transmission electron microscopy of lacrimal gland from KO mice; constitutively active and dominant-negative Rab27b expression; syncollin-GFP secretory protein release assay; actin disruption experiments\",\n      \"journal\": \"American journal of physiology. Cell physiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic KO plus mutagenesis with multiple functional and ultrastructural readouts\",\n      \"pmids\": [\"21525430\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"EPI64B (TBC1D10B) functions as a GTPase-activating protein (GAP) specific for Rab27B in pancreatic acinar cells. EPI64B overexpression almost completely abolishes GTP-Rab27b without affecting GTP-Rab3D, and enhances amylase release in a Rab27B-dependent manner. GAP-dead EPI64B mutations block these effects.\",\n      \"method\": \"Adenoviral overexpression in isolated pancreatic acini; GTP-bound Rab27B pulldown; amylase release assay; Rab27b KO mouse acini for epistasis; site-directed mutagenesis of catalytic residues\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — enzymatic GAP activity demonstrated with mutagenesis and genetic epistasis in relevant cell type\",\n      \"pmids\": [\"23671284\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Rab27b dominant-negative mutants (T23N and N133I) fail to associate with melanosomes and cause redistribution of melanosomes from cell periphery to perinuclear region in melanocytes, implicating Rab27b in outward movement of melanosomes. Wild-type Rab27b co-localizes with TRP-1 and myosin Va at the cell periphery. Dominant-negative Rab27b also reduces dendrite number and length.\",\n      \"method\": \"GFP-tagged WT and dominant-negative Rab27b overexpression in melan-a melanocytes; confocal co-localization with TRP-1 and myosin Va; dendrite morphology analysis; intrinsic GTPase activity assay\",\n      \"journal\": \"The Journal of investigative dermatology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — dominant-negative approach with direct localization readout, but mechanistic specificity limited by dominant-negative artifacts\",\n      \"pmids\": [\"12060386\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Rab27b protein is present at extraordinary high levels (0.1% of total protein) on fusiform vesicles in bladder urothelium and is markedly reduced in cultured urothelial cells that fail to form fusiform vesicles, linking Rab27b expression to fusiform vesicle formation/maintenance.\",\n      \"method\": \"Immuno-electron microscopy; Western blot quantification; comparison of differentiated urothelium vs. de-differentiated cultured cells\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct immuno-EM localization with quantitative expression correlation but no direct loss-of-function\",\n      \"pmids\": [\"14625374\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Slp1 (a Rab27 effector protein) interacts with Rab27B in vivo and co-localizes on zymogen granules in pancreatic acinar cells. Slp1 KO mice show increased number of zymogen granules, implicating the Rab27B–Slp1 complex in amylase secretion.\",\n      \"method\": \"Co-immunoprecipitation of Slp1 and Rab27B; co-localization by immunofluorescence; Slp1 KO mouse morphological analysis\",\n      \"journal\": \"Archives of biochemistry and biophysics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP plus KO mouse phenotype, but functional measurement is morphological rather than direct secretion assay\",\n      \"pmids\": [\"18477466\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Kinesin-1 (Kif5b) is recruited to a Slp3/Rab27b effector complex on mast cell secretory granules in a PI3K-dependent and stimulus-dependent manner. PI3K-dependent formation of the kinesin-1/Slp3/Rab27b complex is required for microtubule-dependent movement of secretory granules toward the exocytic site during mast cell degranulation.\",\n      \"method\": \"Kif5b conditional KO mice; passive systemic anaphylaxis model; BMMC degranulation assays; SG translocation imaging; co-immunoprecipitation of kinesin-1/Slp3/Rab27b; PI3K inhibitor experiments\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic KO with Co-IP defining molecular complex and PI3K-dependence, in vitro and in vivo functional readouts\",\n      \"pmids\": [\"27810912\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Rab27b mediates shear stress-induced vesicular export of miR-143 from endothelial cells downstream of the KLF2 transcription factor. Rab7a and Rab27b are both required for this extracellular vesicle-based miRNA secretion pathway.\",\n      \"method\": \"Rab27b and Rab7a siRNA knockdown; shear stress stimulation; miR-143 vesicular export quantification in endothelial cells\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — siRNA knockdown with functional secretion readout, single lab, single method\",\n      \"pmids\": [\"26348397\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"After beta-adrenergic stimulation in parotid acinar cells, Rab27B translocates from secretory granules to the subapical region (5 min) and then dissociates into the cytosol (30 min) through binding to GDI (GDP dissociation inhibitor), which extracts GDP-bound Rab27B from membranes.\",\n      \"method\": \"Immunofluorescence time-course after isoproterenol treatment; subcellular fractionation; Rab27B-GDI complex detection in cytosol fractions\",\n      \"journal\": \"European journal of oral sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct localization tracking with mechanistic GDI coupling identified, single lab\",\n      \"pmids\": [\"19583748\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"In lacrimal gland acinar cells, RAB27B enrichment occurs early in secretory vesicle formation at a basally-localized 'nascent vesicle site' adjacent to the trans-Golgi network. Transport from this nascent vesicle site to the subapical region requires intact microtubules. RAB27B-enriched vesicles in the subapical cytoplasm acquire Myosin 5C for actin-based motility.\",\n      \"method\": \"YFP-Rab27b live-cell confocal microscopy in rabbit lacrimal gland acinar cells; vesicle pool depletion-repletion protocol; nocodazole treatment; p150Glued co-localization; Myosin 5C co-localization\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — live-cell imaging with functional perturbation revealing biogenesis mechanism, single lab\",\n      \"pmids\": [\"22363735\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Rab27b localizes to tubulovesicle membranes in gastric parietal cells. Upon stimulation, wild-type Rab27b and constitutively active Rab27b Q78L translocate to the apical membrane, while dominant-negative Rab27b N133I does not. Expression of Rab27b N133I almost completely inhibits acid secretion.\",\n      \"method\": \"Mass spectrometry identification in tubulovesicular fractions; YFP-tagged WT, Q78L, N133I adenoviral expression; fluorescence microscopy of resting and stimulated cells; aminopyrine accumulation acid secretion assay\",\n      \"journal\": \"Gastroenterology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — proteomic identification plus mutagenesis with quantitative functional secretion readout\",\n      \"pmids\": [\"20888820\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Rab27b is upregulated in Griscelli syndrome type II melanocytes (lacking Rab27a) and forms a tripartite complex with melanophilin and myosin Va transcripts containing exon F on the melanosome membrane, partially compensating for loss of Rab27a function.\",\n      \"method\": \"Real-time quantitative PCR; Western blot; immunofluorescence co-localization; yeast two-hybrid screening\",\n      \"journal\": \"Pigment cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2/3 — yeast two-hybrid plus immunofluorescence defining tripartite complex, but compensation is partial and mechanistic detail limited\",\n      \"pmids\": [\"15357836\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"RAB27B controls stretch-induced exocytosis of discoidal/fusiform vesicles (DFVs) in bladder umbrella cells. RAB27A-specific shRNA does not inhibit exocytosis. RAB27B operates in a pathway parallel to and independent of the RAB11A-RAB8A-MYO5B pathway.\",\n      \"method\": \"Whole bladder filling preparation; shRNA-mediated knockdown of RAB27B and RAB27A; hGH-loaded DFV exocytosis assay; dominant-active/dominant-negative RAB11A and RAB8A mutants; Squassh segmentation quantification of RAB27B-positive DFVs\",\n      \"journal\": \"American journal of physiology. Cell physiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic loss-of-function with isoform specificity established, epistasis with parallel pathway demonstrated, ex vivo whole-organ functional assay\",\n      \"pmids\": [\"29167152\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Rab27b is required for lysosomal exocytosis and surface expression of proteolipid protein (PLP) in oligodendrocytes. Rab27b KD reduces lysosomal exocytosis, decreases PLP surface expression, and reduces myelin-like membrane formation in neuron co-culture.\",\n      \"method\": \"shRNA knockdown of Rab27b in oligodendrocytes; lysosomal exocytosis assays; PLP surface expression measurement; oligodendrocyte-neuron co-culture myelination assay\",\n      \"journal\": \"Neuroscience bulletin\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KD with multiple functional readouts, single lab\",\n      \"pmids\": [\"27325508\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Rab27b regulates alpha-synuclein release, autophagic clearance, and toxicity in neurons. Rab27b KD increases paracrine αsyn toxicity, shifts released αsyn to higher-molecular-weight species, increases insoluble intracellular αsyn, and impairs autophagic flux (reduced LC3 turnover after chloroquine treatment).\",\n      \"method\": \"shRNA knockdown; paracrine αsyn neuronal model; size-exclusion chromatography of released αsyn; immunofluorescence of LC3 puncta; chloroquine autophagic flux assay; Western blot of insoluble αsyn fractions\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal mechanistic readouts, single lab\",\n      \"pmids\": [\"32350025\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RAB27B controls NRAS palmitoylation and trafficking to the plasma membrane by interacting with ZDHHC9, a palmitoyl acyltransferase. RAB27B depletion selectively abrogates mutant NRAS-mediated ERK signaling and progenitor cell growth in mice, and reduces myelomonocytic leukemia development. RAB27B is upregulated in CBL- or JAK2-mutated myeloid malignancies.\",\n      \"method\": \"Proteomic studies; co-immunoprecipitation of RAB27B and ZDHHC9; Rab27b KO mice with NRAS mutant hematopoietic cells; NRAS palmitoylation assays; ERK signaling assays; in vivo leukemia model; primary human AML RAB27B depletion\",\n      \"journal\": \"The Journal of clinical investigation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP defining interaction plus genetic KO in vivo model with multiple orthogonal mechanistic readouts\",\n      \"pmids\": [\"37317963\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"NRF2 promotes Rab27b expression transcriptionally in urothelial cells, and RAB27B mediates NRF2-dependent UPEC expulsion from urothelial cells. Loss of NRF2 reduces RAB27B expression and impairs UPEC expulsion, increasing bacterial burden both in vitro and in vivo.\",\n      \"method\": \"NRF2 KO and overexpression in urothelial cells; RAB27B expression measurement; UPEC expulsion assays; mouse UTI model; dimethyl fumarate (NRF2 inducer) treatment\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic and pharmacological manipulation with in vitro and in vivo functional readouts, single lab\",\n      \"pmids\": [\"34686330\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"FOXO1 transcriptionally regulates RAB27B expression in kidney proximal tubule cells. In high-glucose conditions (mimicking diabetic kidneys), FOXO1 is phosphorylated and inactivated, leading to RAB27B downregulation and decreased exosome secretion. Constitutively active nonphosphorylatable FOXO1 restores RAB27B and exosome secretion.\",\n      \"method\": \"Bioinformatics identification of FOXO1 binding sites in Rab27b promoter; high-glucose treatment of BUMPT cells; RAB27B overexpression rescue; constitutively active FOXO1 overexpression; diabetic mouse model exosome analysis\",\n      \"journal\": \"Diabetes\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — promoter bioinformatics plus functional rescue experiments in vitro and in vivo mouse model, single lab\",\n      \"pmids\": [\"33597203\"],\n      \"value\": \"FOXO1 transcriptionally activates RAB27B to control exosome secretion\"\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CaSR activates RAB27B through a PI3K/PKA/mTOR/MADD (guanine nucleotide exchange factor) pathway, promoting secretion of cytokines (IL-6, IL-1β, IL-8, IP-10, RANTES) from breast cancer cells. Rab11A interacts with and activates MADD, a GEF for Rab27A/B, linking endocytic recycling endosomes to Rab27B-regulated secretory vesicles via endosomal PI3K (Vps34 and PI3KC2α).\",\n      \"method\": \"CaSR stimulation assays; PI3K/PKA/mTOR/MADD pharmacological inhibition; Co-immunoprecipitation of Rab11A and MADD; cytokine secretion ELISA; siRNA knockdown of pathway components\",\n      \"journal\": \"Cellular signalling\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — Co-IP plus pharmacological dissection defining upstream activation pathway, single lab\",\n      \"pmids\": [\"37604243\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"ZIP4 promotes RAB27B expression through CREB-regulated transcription in pancreatic cancer cells. RAB27B is required for the release of HSP70- and HSP90-associated extracellular vesicles that activate p38 MAPK and induce muscle-wasting gene expression (F-box protein 32, UBR2) in myotubes, causing myofibrillar protein loss and cachexia.\",\n      \"method\": \"ZIP4 shRNA knockdown; CREB inhibition; RAB27B expression measurement; EV isolation and Western blot; C2C12 myotube treatment with conditioned media/EVs; p38 MAPK activation assays; orthotopic pancreatic tumor mouse model\",\n      \"journal\": \"Gastroenterology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic and pharmacological manipulation with mechanistic downstream readouts, in vitro and in vivo, single lab\",\n      \"pmids\": [\"30342032\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"V-ATPase (vacuolar H+-ATPase) activity and subunits (V0a1, V0d1) are required for peripheral localization and size of Rab27B-positive secretory vesicles in breast cancer cells. Inhibition of V-ATPase reduces Rab27B-induced invasion, HSP90α secretion, and MMP-2 activation.\",\n      \"method\": \"Mass spectrometry of GFP-Rab27B vesicles identifying V-ATPase subunits; Western blot validation; bafilomycin A1 inhibition; siRNA knockdown of V0a1 and V0d1; invasion and secretion assays\",\n      \"journal\": \"International journal of cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — proteomics-driven discovery plus siRNA and pharmacological validation, single lab\",\n      \"pmids\": [\"23390068\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"β-catenin/Tcf-4 transcriptional activation of RAB27B expression is required for secretion of exosomes from colorectal cancer stem cells. Exosomal miR-146a-5p cargo promotes stemness by targeting Numb in recipient cells.\",\n      \"method\": \"β-catenin/Tcf-4 transcription factor analysis; RAB27B knockdown; exosome secretion quantification; exosomal RNA sequencing; luciferase reporter and rescue assays\",\n      \"journal\": \"International journal of cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — transcription factor-driven RAB27B regulation with functional exosome secretion readout, single lab\",\n      \"pmids\": [\"30980673\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Rab27b negatively regulates c-kit surface expression in megakaryoblastic cells by promoting autocrine secretion of stem cell factor (SCF). Rab27b knockdown reduces SCF secretion, leading to reduced SCF-induced endolysosomal degradation of c-kit and thus increased c-kit surface expression.\",\n      \"method\": \"shRNA knockdown of Rab27b in CMK cells; c-kit surface expression measurement; SCF secretion assay; bafilomycin lysosome inhibition; flow cytometry\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KD with mechanistic dissection of ligand-receptor axis, single lab\",\n      \"pmids\": [\"22349512\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Rab27b promotes lysosomal function in neurons by supporting lysosomal enzyme maturation and acidic vesicle trafficking. Rab27b KO in neurons causes lysosomal proteolytic defects, enzymatic dysfunction, and exacerbated alpha-synuclein aggregation upon preformed fibril treatment. Rab27b overexpression enhances lysosomal activity and reduces insoluble αsyn accumulation.\",\n      \"method\": \"Rab27b KO mice; primary neuronal cultures; shRNA KD in αsyn-inducible neuronal model; lysosomal enzyme activity assays; lysosomal pH measurement; αsyn preformed fibril treatment; Rab27b overexpression; brain lysate analysis from postmortem human PD/DLB/iLBD tissue\",\n      \"journal\": \"The Journal of neuroscience : the official journal of the Society for Neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic KO plus OE in multiple models with mechanistic lysosomal enzyme readouts and human tissue validation\",\n      \"pmids\": [\"39965930\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"TGF-β suppresses RAB27B transcription via SMAD3, reducing exosome release from breast cancer cells. RAB27B depletion or TGF-β treatment increases quantity and alters protein composition of EVs, producing recomposed EVs that inhibit CD8+ T cell-mediated cancer killing.\",\n      \"method\": \"TGF-β treatment; SMAD3 identification as transcriptional repressor of RAB27B; click chemistry proteomics; RAB27B siRNA; exosome quantification; CD8+ T cell cytotoxicity assay\",\n      \"journal\": \"Journal of extracellular vesicles\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — SMAD3-RAB27B transcriptional mechanism plus EV cargo proteomics with functional immune readout, single lab\",\n      \"pmids\": [\"39723610\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Rab27b KO in hippocampal mossy fiber (MF)-CA3 synapses completely eliminates long-term potentiation (LTP), an effect rescued by lentiviral re-expression of human Rab27b but not GFP. At SC-CA1 synapses, Rab27b KO increases facilitation. Rab27b and Rab3a act synergistically at presynaptic terminals for LTP expression.\",\n      \"method\": \"Rab27b KO mice; electrophysiology at SC-CA1 and DG-MF hippocampal synapses; frequency facilitation measurement; LTP induction; lentiviral rescue with human Rab27b\",\n      \"journal\": \"Physiological reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic KO with electrophysiological readouts and lentiviral rescue confirming specificity, single lab\",\n      \"pmids\": [\"32358861\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Genetic deletion of Rab27B in pancreatic acinar cells reduces the size of zymogen granules and moderately decreases digestive enzyme secretion, revealing a role in zymogen granule maturation distinct from Rab3D.\",\n      \"method\": \"Rab27B KO mouse model; electron microscopy of zymogen granule size; in vitro secretion assays from isolated acini; comparison with Rab3D\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic KO with ultrastructural and functional readouts, single lab\",\n      \"pmids\": [\"26845357\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"KIAA1429 stabilizes RAB27B mRNA through the m6A/YTHDF1 axis in chronic myeloid leukemia cells, promoting RAB27B expression and leukemia cell proliferation and drug efflux. Inhibiting KIAA1429 reduces RAB27B mRNA stability, thereby sensitizing CML cells to imatinib.\",\n      \"method\": \"KIAA1429 knockdown; m6A modification analysis; YTHDF1 interaction; RAB27B mRNA stability assays; proliferation and apoptosis assays; drug resistance assays\",\n      \"journal\": \"Genes & diseases\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — post-transcriptional regulation mechanism with functional readouts, single lab\",\n      \"pmids\": [\"37692484\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In neurons, Rab27b KO in A53T alpha-synuclein transgenic mice increases proteinase-K resistant αsyn and phospho-S129 αsyn in cortex, striatum, and substantia nigra, and increases astrocyte/microglial activation. In AAV αsyn model, Rab27b KO accelerates dopaminergic cell loss in the substantia nigra.\",\n      \"method\": \"Rab27b KO × A53T transgenic double mutant mice; AAV αsyn overexpression mouse model; proteinase-K resistance assay; phospho-αsyn immunohistochemistry; glia activation markers; nigral dopaminergic cell counting\",\n      \"journal\": \"bioRxiv : the preprint server for biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genetic KO in two independent in vivo PD models with mechanistic neuropathology readouts, preprint\",\n      \"pmids\": [\"41509326\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DDX10 physically interacts with Rab27b through phase separation and promotes Rab27b-mediated exosome secretion of PD-L1 in oral squamous cell carcinoma cells, contributing to T cell exhaustion.\",\n      \"method\": \"Co-immunoprecipitation of DDX10 and Rab27b; DDX10 knockdown; exosome PD-L1 quantification; T cell functional assays\",\n      \"journal\": \"Research (Washington, D.C.)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single Co-IP with functional readout, single lab, limited mechanistic depth on phase separation\",\n      \"pmids\": [\"40352946\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Rab27b in neurons is required for amyloid beta (Aβ) secretion via lysosomal exocytosis in hiPSC-derived neurons. Silencing Rab27b (or Munc13-4) significantly reduces lysosomal fusion events at the plasma membrane and blocks Aβ release into the extracellular space, as visualized by TIRF microscopy.\",\n      \"method\": \"TIRF microscopy of lysosome-plasma membrane fusion events in hiPSC-derived neurons; siRNA knockdown of Rab27b and Munc13-4; nanoscale flow cytometry of released particles\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct TIRF visualization of lysosomal exocytosis events plus siRNA loss-of-function with quantitative Aβ secretion readout, preprint\",\n      \"pmids\": [\"bio_10.1101_2025.03.01.640950\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"RAB27B is a small GTPase that controls multiple regulated exocytic pathways by docking multivesicular endosomes and secretory/lysosomal granules at the plasma membrane; it acts through GTP/GDP cycling (with EPI64B as a specific GAP and MADD as a GEF), recruits effectors such as Slac2-c/MyRIP, Slp1, Slp3, and Munc13-4 to link granules to actin and microtubule motors, regulates NRAS palmitoylation via interaction with ZDHHC9 to control RAS membrane trafficking and signaling, and promotes lysosomal function and autophagic clearance of alpha-synuclein in neurons, with its transcription regulated by NF-E2, FOXO1, NRF2, β-catenin/Tcf-4, SMAD3, and CREB in a cell-type-specific manner.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"RAB27B is a small GTPase that functions as a master regulator of regulated exocytosis, controlling the docking, maturation, and fusion of secretory granules, lysosome-related organelles, and multivesicular endosomes with the plasma membrane across a remarkably broad range of cell types including platelets, mast cells, neutrophils, exocrine acinar cells, parietal cells, neurons, melanocytes, and urothelial cells [PMID:17384153, PMID:19966785, PMID:15039459, PMID:20888820, PMID:29167152]. RAB27B cycles between GTP-bound active and GDP-bound inactive states regulated by the GAP EPI64B and the GEF MADD, and recruits effector proteins including Slac2-b/EXPH5, Slac2-c/MyRIP, Slp1, Slp3, and Munc13-4 that couple vesicles to actin- and microtubule-based motors for polarized transport to the exocytic site [PMID:23671284, PMID:37604243, PMID:15039459, PMID:27810912, PMID:23281710]. Beyond canonical secretion, RAB27B controls NRAS palmitoylation and plasma membrane trafficking through interaction with the palmitoyl acyltransferase ZDHHC9, thereby regulating RAS-ERK signaling in hematopoietic cells, and promotes lysosomal enzyme maturation and autophagic clearance of alpha-synuclein in neurons, with its loss exacerbating synucleinopathy and dopaminergic neurodegeneration in vivo [PMID:37317963, PMID:39965930, PMID:32350025]. RAB27B transcription is regulated in a cell-type-specific manner by NF-E2 in megakaryocytes, FOXO1 in kidney tubular cells, NRF2 in urothelium, β-catenin/Tcf-4 in colorectal cells, SMAD3 in breast cancer, and CREB downstream of ZIP4 in pancreatic cancer [PMID:12907454, PMID:33597203, PMID:34686330, PMID:30980673, PMID:39723610, PMID:30342032].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Initial evidence placed RAB27B on secretory organelles and implicated its GTPase cycle in regulated secretion, establishing it as a functional paralog of RAB27A in endocrine cells and melanocytes.\",\n      \"evidence\": \"Dominant-negative Rab27b mutants inhibited ACTH secretion in pituitary AtT20 cells and redistributed melanosomes to the perinuclear region in melanocytes; Co-IP showed association with the effector granuphilin\",\n      \"pmids\": [\"11956164\", \"12060386\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No loss-of-function genetic model yet\", \"Effector repertoire largely unknown\", \"Mechanism of membrane association unclear\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"RAB27B was shown to localize to multiple granule types in megakaryocytes and fusiform vesicles in urothelium, and its transcription was found to be NF-E2-dependent, revealing tissue-specific transcriptional control of the regulated secretory machinery.\",\n      \"evidence\": \"ChIP demonstrated NF-E2 occupancy at the Rab27b promoter in megakaryocytes; dominant-negative Rab27 impaired proplatelet formation; immuno-EM placed Rab27b on fusiform vesicles in bladder urothelium\",\n      \"pmids\": [\"12907454\", \"14625374\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No Rab27b knockout mouse yet to confirm megakaryocyte phenotype in vivo\", \"Functional role in urothelium inferred from localization, not direct loss-of-function\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"The identification of Slac2-c/MyRIP as a direct RAB27B effector on exocrine secretory granules established the paradigm of RAB27B recruiting linker proteins to couple granules to cytoskeletal motors for regulated exocytosis.\",\n      \"evidence\": \"Co-IP and immunohistochemistry in parotid acinar cells; functional blocking with recombinant SHD domain and antibodies inhibited amylase release; Rab27b GTP/GDP cycling mutants modulated pancreatic amylase secretion\",\n      \"pmids\": [\"15039459\", \"15451418\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity of actin/microtubule motors downstream of Slac2-c not yet defined\", \"Relative contributions of effectors in exocrine cells unknown\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Genetic knockout studies in mice established RAB27B as essential for platelet dense granule biogenesis, mast cell degranulation, and polarized delivery of secretory granules to the plasma membrane in pituitary cells, confirming non-redundancy with RAB27A.\",\n      \"evidence\": \"Rab27b KO mice showed hemorrhagic disease, reduced dense granules, and impaired platelet aggregation; double KO pituitary cells lost polarized granule distribution; Rab27b KO mast cells showed impaired degranulation and increased microtubule-based granule movement\",\n      \"pmids\": [\"17384153\", \"17761531\", \"17587407\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Effector identity mediating platelet-specific vs. mast cell-specific functions not yet resolved\", \"How Rab27b regulates granule number (biogenesis) vs. docking not mechanistically separated\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"The crystal structure of Rab27b-GDP revealed an unusually open switch region conformation with high flexibility, providing a structural basis for understanding its distinct effector recognition properties.\",\n      \"evidence\": \"X-ray crystallography in three crystal forms plus SAXS solution measurements of mouse Rab27b-GDP\",\n      \"pmids\": [\"17582168\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structure of GTP-bound form\", \"No co-crystal with any effector\", \"Structural basis of Rab27a vs. Rab27b effector selectivity unresolved\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"RAB27B was shown to control multivesicular endosome docking at the plasma membrane for exosome secretion, expanding its role beyond classical secretory granule exocytosis to the exosome biogenesis pathway.\",\n      \"evidence\": \"RNAi screen in HeLa cells; Rab27b silencing redistributed MVEs to perinuclear region and reduced exosome secretion; effector Slac2-b phenocopied the knockdown\",\n      \"pmids\": [\"19966785\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"MVE docking mechanism and fusion machinery downstream of Rab27b unknown\", \"Whether Rab27b selects specific MVE cargo for exosomal release unclear\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"RAB27B was identified as an abundant synaptic vesicle protein that, unlike Rab3a, remains membrane-associated after exocytosis and resists GDI extraction, revealing a distinct recycling mechanism at presynaptic terminals.\",\n      \"evidence\": \"Quantitative iTRAQ proteomics and immunoblotting of purified synaptic vesicles; GDI extraction assay; manipulation of GTP/GDP switch impaired SV recycling\",\n      \"pmids\": [\"20926670\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional redundancy with Rab3a at the synapse not yet genetically dissected\", \"Effectors mediating Rab27b function at the synapse not identified\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"RAB27B was found to promote breast cancer invasion by delivering HSP90α-containing vesicles whose secretion activates extracellular MMP-2, linking its vesicle trafficking function to tumor progression.\",\n      \"evidence\": \"GFP-RAB27B vesicle proteomics identified HSP90α cargo; siRNA, GTP-binding and geranylgeranylation mutants reduced invasion; orthotopic xenograft confirmed in vivo relevance\",\n      \"pmids\": [\"20484105\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How RAB27B vesicle cargo is selected unknown\", \"Whether V-ATPase role is direct or indirect unclear\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Genetic epistasis in mast cells resolved the division of labor between RAB27A and RAB27B: RAB27A/melanophilin/MyoVa controls cortical actin remodeling, while RAB27B/Munc13-4 directly mediates granule exocytosis, and EPI64B was identified as a RAB27B-specific GAP.\",\n      \"evidence\": \"Epistasis across ashen, Rab27b KO, double KO, leaden, dilute, and jinx mouse mast cells; EPI64B GAP activity shown by GTP-Rab27b pulldown with catalytic-dead mutagenesis in pancreatic acini\",\n      \"pmids\": [\"23281710\", \"23671284\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether EPI64B is the sole GAP for Rab27b unknown\", \"How Munc13-4 couples to SNARE-mediated fusion not resolved\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"The Kif5b/Slp3/Rab27b complex was defined as the PI3K-dependent machinery linking secretory granules to kinesin-1 for microtubule-based transport to the exocytic site, explaining how Rab27b coordinates the switch from microtubule to actin-based motility.\",\n      \"evidence\": \"Kif5b conditional KO mice; Co-IP of kinesin-1/Slp3/Rab27b; PI3K inhibitor disrupted complex assembly; passive systemic anaphylaxis and BMMC degranulation assays\",\n      \"pmids\": [\"27810912\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How PI3K signal triggers kinesin-1 recruitment to Slp3 mechanistically unclear\", \"Whether this complex operates in cell types beyond mast cells untested\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"RAB27B was discovered to regulate autophagic clearance and lysosomal function in neurons, with its loss causing accumulation of insoluble alpha-synuclein and increased paracrine toxicity, and to be essential for hippocampal long-term potentiation.\",\n      \"evidence\": \"shRNA KD in neuronal α-syn model showed impaired LC3 turnover and increased insoluble α-syn; Rab27b KO mice completely lost MF-CA3 LTP, rescued by lentiviral human Rab27b re-expression\",\n      \"pmids\": [\"32350025\", \"32358861\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic link between Rab27b and autophagosome-lysosome fusion not established\", \"Effector mediating LTP function unknown\", \"Single-lab findings for each\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"RAB27B was shown to control NRAS palmitoylation and plasma membrane trafficking by interacting with the palmitoyl acyltransferase ZDHHC9, establishing a non-canonical function in RAS signaling regulation distinct from vesicle exocytosis.\",\n      \"evidence\": \"Co-IP of RAB27B and ZDHHC9; Rab27b KO mice with NRAS-mutant hematopoietic cells showed abrogated ERK signaling and reduced leukemia development; NRAS palmitoylation assays\",\n      \"pmids\": [\"37317963\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether RAB27B regulates palmitoylation of other substrates beyond NRAS unknown\", \"Structural basis of RAB27B-ZDHHC9 interaction undefined\", \"Whether this function is GTP-dependent not shown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Rab27b was established as essential for lysosomal enzyme maturation in neurons, with its genetic deletion causing lysosomal proteolytic defects and exacerbating alpha-synuclein aggregation and dopaminergic neurodegeneration in multiple in vivo Parkinson's disease models.\",\n      \"evidence\": \"Rab27b KO mouse neurons with lysosomal enzyme activity assays and pH measurements; A53T transgenic × Rab27b KO and AAV α-syn models showing increased PK-resistant α-syn and nigral cell loss; human PD/DLB brain tissue analysis\",\n      \"pmids\": [\"39965930\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether Rab27b loss is causally linked to human PD remains correlative\", \"Specific lysosomal trafficking step regulated by Rab27b in neurons not defined\", \"Effector mediating neuronal lysosomal function unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include the structural basis of Rab27b effector selectivity versus Rab27a, the full effector code in each cell type, whether the ZDHHC9-mediated RAS palmitoylation function extends to other substrates, and whether Rab27b loss contributes causally to human neurodegenerative disease.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No co-crystal structure of Rab27b with any effector\", \"Comprehensive cell-type-specific effector mapping lacking\", \"Causal link to human Parkinson's disease not established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003924\", \"supporting_discovery_ids\": [6, 14, 17]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [0, 2, 6, 8, 10, 24, 25, 27]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 9, 25, 27]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [23]},\n      {\"term_id\": \"GO:0005764\", \"supporting_discovery_ids\": [13, 28, 38, 45]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 2, 6, 9, 10, 16, 25, 27]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [4, 9, 12]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [30, 33]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [11, 40]},\n      {\"term_id\": \"R-HSA-109582\", \"supporting_discovery_ids\": [1, 7]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [29, 38]}\n    ],\n    \"complexes\": [\n      \"Rab27b–Slac2-c/MyRIP\",\n      \"Rab27b–Munc13-4\",\n      \"Kif5b–Slp3–Rab27b\",\n      \"Rab27b–ZDHHC9\"\n    ],\n    \"partners\": [\n      \"EXPH5\",\n      \"SYTL1\",\n      \"UNC13D\",\n      \"SYTL3\",\n      \"MYO5A\",\n      \"ZDHHC9\",\n      \"TBC1D10B\",\n      \"MADD\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}