Affinage

RAB18

Ras-related protein Rab-18 · UniProt Q9NP72

Length
206 aa
Mass
23.0 kDa
Annotated
2026-06-10
66 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB18 is a small GTPase that cycles between an inactive GDP-bound state and an active, membrane-anchored GTP-bound state to coordinate lipid droplet (LD) biology, ER architecture, and membrane trafficking (PMID:15914536, PMID:21473985). Its activation requires the RAB3GAP1/RAB3GAP2 heterodimeric GEF, which targets RAB18 to the ER and is necessary for proper ER tubule/sheet morphology, while the TRAPPII complex provides a second GEF activity that drives COPI-dependent recruitment of RAB18 to LD surfaces; the GAP TBC1D20 cycles RAB18 off ER membranes (PMID:24891604, PMID:28003315, PMID:26063829). Active RAB18 localizes to the ER and the phospholipid monolayer of LDs (PMID:16207721), where it controls LD growth by tethering ER to LDs through binding the ER-associated NRZ (NAG-RINT1-ZW10) complex and its associated SNAREs (Syntaxin18, Use1, BNIP1), so that loss of RAB18 reduces mature LD numbers and lipid storage and elevates ER stress (PMID:29367353). At the LD it scaffolds lipid-metabolic machinery — interacting with PLIN2 and ACSL3 in a tripartite complex, recruiting ATGL via the Arf/GBF1 system, and bridging to HSPA8/PLIN2 in chaperone-mediated lipolysis — thereby governing triacylglycerol storage and lipolysis in adipocytes, hepatic stellate cells, and myoblasts (PMID:33713834, PMID:31610914, PMID:38607975). RAB18 also functions in sterol mobilization at membrane contact sites, where its loss perturbs cholesterol precursor handling involving EBP and ORP2 (PMID:37774976), in ER-to-Golgi retrograde trafficking and Golgi integrity (PMID:18664496), and in autophagy/lysosomal maturation through RAB3GAP-dependent engagement of the Vps34/Beclin1 complex and crosstalk with RAB7 (PMID:28342870, PMID:32248620, PMID:30721447). In neurons it supports radial migration by limiting lysosomal degradation of N-cadherin (PMID:26879639), and it drives focal adhesion maturation and directional migration via kinectin-1-dependent anterograde ER transport (PMID:32525992). Loss-of-function mutations in RAB18 that abolish guanine-nucleotide binding cause Warburg Micro syndrome (PMID:21473985). RAB18 is co-opted by multiple viruses, binding nonstructural proteins of HCV, DENV, and CSFV in a GTP-dependent manner and acting as a host factor for BKPyV, to support replication and assembly at LD-ER interfaces (PMID:23935497, PMID:24696471, PMID:32419589, PMID:28815213).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2005 High

    Establishing where RAB18 acts: the initial question was the subcellular site and nucleotide-state dependence of RAB18 function, answered by showing it decorates the LD monolayer and drives ER-LD apposition.

    Evidence LD proteomics, immunoelectron microscopy, and dominant-active/negative mutants in HepG2 cells and adipocytes

    PMID:15914536 PMID:16207721

    Open questions at the time
    • Did not identify the tethering machinery linking ER to LDs
    • Did not establish the GEF/GAP regulating RAB18 activation
  2. 2007 High

    Extending RAB18 beyond LDs: tested whether RAB18 had roles in regulated secretion, showing activation-dependent association with secretory granules that inhibits exocytosis.

    Evidence Immunoelectron microscopy and secretion assays with GTPase mutants in PC12 and AtT20 neuroendocrine cells

    PMID:17488286

    Open questions at the time
    • Effector mediating secretory inhibition not identified
    • Relationship to LD function unresolved
  3. 2008 High

    Asked whether RAB18 controls early secretory membrane trafficking, revealing a role in Golgi integrity and selective COPI-independent Golgi-to-ER retrograde transport.

    Evidence siRNA, dominant-negative mutants, and live-cell cargo transport/photobleach assays

    PMID:18664496

    Open questions at the time
    • Tethers/SNAREs at the Golgi-ER step not defined
    • How this relates to LD function unclear
  4. 2011 High

    Connected RAB18 to human disease and to insulin signaling: nucleotide-null mutations cause Warburg Micro syndrome, and PI3K-dependent recruitment links RAB18 to lipogenesis as well as lipolysis.

    Evidence Autozygosity mapping with nucleotide-binding assays and zebrafish knockdown; PI3K inhibition with gain/loss-of-function in 3T3-L1 adipocytes

    PMID:21473985 PMID:21829560

    Open questions at the time
    • Molecular cause of the developmental/disease phenotype not mechanistically resolved
    • How a single GTPase mediates both lipogenesis and lipolysis unexplained
  5. 2014 High

    Identified the activation machinery: RAB3GAP1/2 is the RAB18 GEF that controls ER targeting and ER morphology, linking disease mutations in the GEF to loss of RAB18 activation.

    Evidence Direct GEF activity assay, fractionation, ER-marker imaging, and disease-mutant analysis

    PMID:24891604

    Open questions at the time
    • Did not address whether other GEFs act on RAB18 at the LD
    • Downstream effectors of activated RAB18 not defined
  6. 2014 High

    Established RAB18 as a virally hijacked host factor: GTP-dependent binding to HCV NS5A and DENV-related FASN recruitment route replicase/lipid machinery to LD-ER sites.

    Evidence Reciprocal co-IP with GTP/GDP-locked mutants, colocalization, and knockdown/overexpression with viral output in HCV- and DENV-infected cells

    PMID:23935497 PMID:24696471 PMID:24997429

    Open questions at the time
    • Whether virus exploits native ER-LD tethering function not directly tested
    • Structural basis of NS5A binding unresolved
  7. 2015 Medium

    Completed the GTPase cycle and broadened physiology: TBC1D20 is the RAB18 GAP that cycles it off the ER, and RAB18 activity/prenylation drives LD loss during hepatic stellate cell activation.

    Evidence In vitro GAP assay with fractionation in TBC1D20-null cells; functional GTPase/prenylation mutants and knockdown in hepatic stellate cells

    PMID:25482505 PMID:26063829

    Open questions at the time
    • GAP activity was modest in vitro
    • Whether stellate-cell LD loss uses tethering or lipolytic effectors not defined
  8. 2016 Medium

    Resolved how RAB18 reaches LDs and acts in neurons: TRAPPII (delivered via COPI) is a second GEF activating RAB18 at LDs, and in cortex RAB18 supports radial migration by protecting surface N-cadherin from lysosomal degradation.

    Evidence GEF assay with CRISPR/siRNA and LD morphology; in utero electroporation with N-cadherin and lysosomal-inhibitor follow-up

    PMID:26879639 PMID:28003315

    Open questions at the time
    • How two GEFs (RAB3GAP vs TRAPPII) partition RAB18 between ER and LD pools unclear
    • Mechanism by which RAB18 limits N-cadherin degradation undefined
  9. 2017 Medium

    Linked RAB18 to autophagy/proteostasis and a further virus: RAB18 promotes macroautophagy via its RAB3GAP GEFs, and it is an essential host factor for BKPyV retrograde transport with the NRZ complex.

    Evidence Autophagy flux assays with RAB3GAP epistasis in fibroblasts; genome-wide siRNA screen with validation in renal epithelial cells

    PMID:28342870 PMID:28815213

    Open questions at the time
    • Direct autophagy effectors of RAB18 not yet identified
    • Whether BKPyV transport uses the same NRZ tether as LDs not directly shown
  10. 2018 High

    Delivered the central mechanism: activated RAB18 tethers ER to LDs by binding the NRZ complex and its SNAREs, defining how RAB18 drives LD growth — though one cell type showed only modest LD phenotypes, indicating context dependence.

    Evidence Co-IP/pulldown of RAB18-NRZ-SNARE complex and CRISPR/siRNA with LD/ER-stress readouts; contrasting CRISPR knockout in mammary carcinoma cells

    PMID:29367353 PMID:29949452

    Open questions at the time
    • Basis of cell-type-specific dependence on RAB18 for LDs unresolved
    • How tethering is coupled to lipid transfer not directly demonstrated
  11. 2019 Medium

    Mapped RAB18's lipolytic and autophagic outputs: it acts upstream of ATGL via Arf/GBF1, supplies LD-derived lipids for autophagosome formation (triggering ATG9A-based compensation), and partners with RAB7 in neuronal lysosomal transport.

    Evidence Dominant-negative localization assays for ATGL/Arf4; RAB18 knockout with lipidomics/phosphoproteomics; co-IP/fractionation and KO neuron phenotypes with RAB7

    PMID:30721447 PMID:31610914 PMID:31874152

    Open questions at the time
    • Direct vs indirect nature of RAB18-RAB7 relationship unclear
    • ATGL recruitment mechanism inferred from dominant-negative phenotype only
  12. 2020 Medium

    Expanded the effector repertoire: GTP-RAB18 binds Atg6/Beclin1 to promote autolysosome maturation via Vps34 Complex I, interacts with kinectin-1 to drive kinesin-1-dependent ER transport for focal adhesion maturation, and binds CSFV NS5A.

    Evidence GTP-state co-IPs and Drosophila epistasis; co-IP with kinectin-1, TIRF FA imaging and chemotaxis; co-IP/GST-pulldown with viral knockdown

    PMID:32248620 PMID:32419589 PMID:32525992

    Open questions at the time
    • Whether these effector interactions occur simultaneously or in distinct RAB18 pools unknown
    • Beclin1 finding from Drosophila not confirmed in mammals
  13. 2021 Medium

    Defined the LD-resident effector scaffold: RAB18 forms a PLIN2-ACSL3 complex on LDs, with PLIN2 required for RAB18 LD localization and RAB18 promoting ACSL3 recruitment, controlling TAG storage.

    Evidence Co-IP, PLIN2/ACSL3 knockdown, and TAG/LD morphology readouts in C2C12 myoblasts

    PMID:33713834

    Open questions at the time
    • Order of assembly of the RAB18-PLIN2-ACSL3 complex unresolved
    • Whether ACSL3 fatty-acid activation is directly regulated not shown
  14. 2023 High

    Broadened RAB18 into sterol biology and ubiquitin signaling: GEF-dependent interactomics linked RAB18 to EBP/ORP2-dependent cholesterol biosynthesis at contact sites, and RAB18 recruits the CSN7A-CRL3 complex to LDs to drive adipogenesis.

    Evidence BioID with validation co-IPs and cholesterol-precursor mass spectrometry in KO cells and patient fibroblasts; co-IP and knockdown with adipogenesis/neddylation assays

    PMID:37091236 PMID:37774976

    Open questions at the time
    • Mechanism by which RAB18 promotes sterol transfer not biochemically reconstituted
    • Substrate of LD-localized CRL3 not identified
  15. 2024 Medium

    Identified a novel activation cue and a CMA function: 2'3'-cGAMP binds RAB18 and promotes GTP loading to drive a FosB migration axis, while RAB18 bridges HSPA8 and PLIN2 in chaperone-mediated lipolysis upregulated during PRRSV-2 infection.

    Evidence cGAMP pulldown/GTP-loading assays with FosB reporter and migration assays; co-IP/domain mapping with HSPA8/PLIN2/LAMP2A and NF-kB pathway dissection

    PMID:38607975 PMID:39413198

    Open questions at the time
    • Physiological significance of cGAMP-driven RAB18 activation outside migration unclear
    • Whether CMA-lipolysis function is conserved beyond infection context untested
  16. 2025 Low

    Probed a ciliary role: GTP-RAB18 at basal bodies recruits the BBSome for ciliary entry in Chlamydomonas, suggesting a trafficking function in cilia.

    Evidence Localization and GTPase-state mutants with BBSome colocalization/ciliary-entry assays in Chlamydomonas (preprint)

    PMID:bio_10.1101_2025.02.04.636545

    Open questions at the time
    • Preprint not peer-reviewed and without biochemical reconstitution
    • Relevance of this ciliary role to mammalian RAB18 unestablished

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many RAB18 functions (ER-LD tethering, lipolysis, sterol transfer, autophagy, migration, viral hijacking) are partitioned across distinct activation cues, GEFs, and effector pools within a cell remains unresolved.
  • No structural model defining how RAB18 selects among NRZ, PLIN2/ACSL3, kinectin-1, Beclin1, and EBP/ORP2 effectors
  • Mechanism coupling RAB18-mediated tethering to actual lipid/sterol transfer not reconstituted
  • Determinants directing RAB18 between RAB3GAP/ER and TRAPPII/LD activation undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005811 lipid droplet 4 GO:0005783 endoplasmic reticulum 3 GO:0005764 lysosome 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-9612973 Autophagy 3 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-1643685 Disease 1
Partners
ACSL3HSPA8KTN1PLIN2RAB3GAP1RAB3GAP2RAB7TBC1D20
Complex memberships
RAB18-PLIN2-ACSL3 complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Rab18 localizes to lipid droplets (LDs) in HepG2 cells; wild-type and dominant-active Rab18 localize to LDs but the dominant-negative form does not. Rab18 overexpression induces close apposition of LDs to rough ER-derived membrane cisternae (termed LD-associated membrane, LAM), and this is linked to a decrease in ADRP on LDs. Proteomic analysis of LD fraction, immunohistochemistry, western blotting, dominant-active/dominant-negative mutant expression, RNA interference, brefeldin A treatment Journal of cell science High 15914536
2005 GFP-Rab18 localizes directly to the phospholipid monolayer surface of LDs (shown by immunoelectron microscopy), and this association is increased upon lipolytic stimulation of adipocytes by beta-adrenergic agonists. A caveolin-3 truncation mutant that inhibits LD catabolism labels mutually exclusive LD subpopulations from Rab18-labeled LDs. GFP tagging, immunoelectron microscopy, lipolytic stimulation, beta-adrenergic antagonist reversal, co-expression of caveolin-3 mutant The Journal of biological chemistry High 16207721
2007 In neuroendocrine cells (PC12 and AtT20), Rab18 associates with a subpopulation of secretory granules upon stimulation of the regulated secretory pathway, and this association is linked to inhibition of secretory activity. Dominant-active Rab18 associates with secretory granules; dominant-inactive Rab18 remains cytosolic. Immunofluorescence, immunoelectron microscopy, dominant-active/dominant-negative mutant expression, secretion assays in PC12 and AtT20 cells Traffic (Copenhagen, Denmark) High 17488286
2008 Rab18 overexpression or siRNA knockdown severely disrupts the Golgi complex and reduces secretion of VSVG. Rab18 mutants specifically enhance retrograde COPI-independent Golgi-to-ER transport of beta-1,4-galactosyltransferase-YFP but not COPI-dependent p58-YFP cargo. Rab18-S22N potentiates BFA-induced ER-Golgi fusion, indicating a role for Rab18 in ER-Golgi trafficking. siRNA knockdown, dominant-negative mutant expression, VSVG-GFP secretion assay, photobleach assay for retrograde Golgi-ER transport, BFA treatment Journal of cell science High 18664496
2011 Loss-of-function mutations in RAB18 (Leu24Gln and Arg93del) cause Warburg Micro syndrome. Nucleotide binding assays showed these mutant proteins are functionally null — unable to bind guanine nucleotides. Knockdown of rab18 in zebrafish confirmed a conserved developmental role. Autozygosity mapping, Sanger sequencing, MLPA, nucleotide binding assays, zebrafish rab18 knockdown American journal of human genetics High 21473985
2011 Insulin induces Rab18 recruitment to LD surfaces via phosphatidylinositol 3-kinase (PI3K) signaling in 3T3-L1 adipocytes. Rab18 overexpression increases basal lipogenesis, and Rab18 silencing impairs the lipogenic response to insulin, establishing Rab18 as a mediator of insulin-stimulated lipogenesis as well as beta-adrenergic lipolysis. PI3K inhibitor treatment, Rab18 overexpression, siRNA silencing, lipogenesis assays in 3T3-L1 adipocytes PloS one Medium 21829560
2013 Rab18 binds to the HCV nonstructural protein NS5A; GTP-bound (active) Rab18 binds NS5A more strongly than constitutively GDP-bound Rab18. Rab18 promotes physical association of NS5A and other replicase components with LDs in HCV-infected cells and modulates HCV genome replication and production of infectious virions. Unbiased proteomics, co-immunoprecipitation, GTP/GDP-locked Rab18 mutant binding assays, colocalization studies in HCV-infected cells, Rab18 knockdown/overexpression with viral output measurement PLoS pathogens High 23935497
2014 The Rab3GAP complex (RAB3GAP1/RAB3GAP2 heterodimer) is a specific guanine nucleotide exchange factor (GEF) for Rab18. Rab3GAP localizes to the ER and is necessary and sufficient for ER targeting of Rab18. In the absence of Rab3GAP or Rab18 function, ER tubular networks (marked by reticulon 4) are disrupted and ER sheets (CLIMP-63) spread into the cell periphery. Disease-associated point mutations in Rab3GAP1 (T18P, E24V) and Rab3GAP2 (R426C) abolish GEF and membrane-targeting activities. GEF activity assay, subcellular fractionation, immunofluorescence with ER markers, dominant-negative and disease mutants, siRNA knockdown, Rab18 membrane recruitment assay The Journal of cell biology High 24891604
2014 Active (GTP-bound) Rab18 is required for targeting of fatty acid synthase (FASN) to ER and LD sites of dengue virus (DENV) replication. The interaction of FASN with DENV NS3 protein depends on conversion of Rab18 from GDP- to GTP-bound form. Inactive Rab18 or Rab18 knockdown reduces DENV replication, viral protein/RNA production, and LD induction. GTP/GDP-locked Rab18 mutant expression, siRNA knockdown, colocalization, co-immunoprecipitation, viral output measurement (RNA, protein, progeny) Journal of virology High 24696471
2014 Rab18 is required for trafficking of the HCV core protein to LDs for viral assembly. Rab18 knockdown reduces intracellular and extracellular viral infectivity but not intracellular viral replication, and blocks recruitment of the HCV core protein to LDs. Rab18 overexpression increases extracellular viral infectivity ~2-fold. Rab18 siRNA knockdown, Rab18 overexpression, colocalization of Rab18 with core protein, viral infectivity assays Virology Medium 24997429
2015 TBC1D20 shows RAB18 GTPase-activating protein (GAP) activity in vitro and is a physiological substrate regulator of RAB18. In cells lacking TBC1D20, RAB18 becomes more stably ER-associated and less cytosolic, indicating TBC1D20 promotes RAB18 cycling off the ER membrane. This establishes RAB18 as a substrate of TBC1D20. In vitro GAP activity assay, subcellular fractionation, immunofluorescence of RAB18 localization in TBC1D20-null cells Open biology Medium 26063829
2015 In hepatic stellate cells, Rab18 GTPase activity and isoprenylation are required for stellate cell LD loss and activation marker induction. Rab18 knockdown retards LD loss and blocks activation; Rab18 mRNA and protein increase during activation. Rab18 is identified as a retinoic acid-responsive, LD-associated protein in HSCs. siRNA knockdown, plasmid overexpression, functional mutants (GTPase-dead and isoprenylation-defective), gene array, immunocytochemistry, in vivo liver injury model Hepatology (Baltimore, Md.) Medium 25482505
2016 Mammalian TRAPPII complex acts as a GEF for both Rab18 and Rab1. Inactivation of TRAPPII-specific subunits (siRNA or CRISPR-Cas9 deletion) impairs Rab18 recruitment to LD surfaces and results in aberrantly large LDs with reduced lipolysis. The COPI-TRAPPII interaction is required for Rab18 recruitment to LDs, suggesting COPI brings TRAPPII to the LD surface where TRAPPII activates Rab18. GEF activity assay, siRNA depletion, CRISPR-Cas9 deletion, LD morphology analysis, Rab18 localization assay The EMBO journal High 28003315
2016 In developing mouse cerebral cortex, RAB18 regulates neuronal radial migration and morphogenesis. Suppression of RAB18 by in utero electroporation, or overexpression of dominant-negative RAB18, impairs radial migration. Loss of RAB18 accelerates N-cadherin degradation via the lysosomal pathway, reducing surface N-cadherin levels on neurons. In utero electroporation (shRNA knockdown and dominant-negative overexpression), in vitro neurite growth assays, N-cadherin surface level measurement, lysosomal inhibitor treatment Molecular brain Medium 26879639
2017 RAB18 positively modulates macroautophagy in primary human fibroblasts; knockdown reduces autophagic activity while overexpression enhances it. This function depends on RAB3GAP1 and RAB3GAP2 as GEFs. RAB18 knockdown also impairs proteostasis, causing accumulation of ubiquitinated proteins. siRNA knockdown, overexpression, autophagy flux assays, ubiquitinated protein accumulation measurement, RAB3GAP1/2 co-knockdown epistasis Biochemical and biophysical research communications Medium 28342870
2017 Rab18 is required for BK polyomavirus (BKPyV) infection; genome-wide siRNA screen and follow-up identified Rab18 and syntaxin 18 as essential host factors. Rab18 and the NRZ complex function in retrograde transport of BKPyV from late endosomes to the ER lumen. Whole-genome siRNA screen, siRNA knockdown validation, viral infection assays in primary human renal proximal tubule epithelial cells mSphere Medium 28815213
2018 Rab18 controls LD growth and maturation by tethering the ER to LDs. LD-associated Rab18 (activated by its GEF Rab3GAP1/2) binds specifically to the ER-associated NRZ (NAG-RINT1-ZW10) tethering complex and associated SNAREs (Syntaxin18, Use1, BNIP1), recruiting ER to LDs and forming direct ER-LD contacts. Rab18 deficiency or NRZ/SNARE defects cause drastically reduced mature LD numbers, decreased lipid storage, and increased ER stress. Co-immunoprecipitation, pulldown assays, CRISPR/siRNA knockdown of Rab18 and NRZ/SNARE components, LD morphology and lipid quantification, ER stress markers The Journal of cell biology High 29367353
2018 In human mammary carcinoma cells, Rab18 localizes to the ER and LD membranes in an activation-state-dependent manner, but knockout of Rab18 causes only modest reductions in LD size and numbers with no evidence for essential roles in LD formation, LD turnover on starvation, or targeting of several LD proteins. Rab18 knockout (CRISPR), LD morphology quantification, protein targeting assays, starvation-induced LD turnover Molecular biology of the cell Medium 29949452
2019 RAB18 knockout impairs lipid droplet catabolism and fatty acid release, reducing lipid availability for autophagosome formation. Compensatory adaptations include increased ATG2B expression and phosphorylation, increased ATG12-ATG5 conjugate formation, and enhanced ATG9A phosphorylation at Y8 and S14, which increases ATG9A trafficking. Y8 phosphorylation of ATG9A is important to maintain basal autophagy under RAB18 knockout conditions. RAB18 knockout, autophagy flux assays, lipidomics, phosphoproteomics, pharmacological inhibition of Y8 phosphorylation, ATG9A trafficking assays Journal of molecular biology Medium 31874152
2019 In neurons, Rab18 associates with lysosomes, actively traffics along neurites, and colocalizes/cofractionates/coprecipitates with Rab7. Rab18-deficient neurons show impaired lysosomal transport and aberrant autophagy. Rab7 is upregulated in Rab18-deficient neurons, suggesting compensatory regulation between Rab18 and Rab7 in lysosomal/autophagic activities. Immunofluorescence, subcellular fractionation, co-immunoprecipitation, live-cell imaging of lysosomal transport, autophagosome marker assays, Rab18-/- mouse model, electron microscopy Molecular neurobiology Medium 30721447
2020 GTP-bound Rab18 (in Drosophila) binds Atg6/Beclin1, a permanent subunit of Vps34 complexes. The Rab3GAP-Rab18 module promotes autolysosome maturation through interaction with Vps34 Complex I. Loss of Rab3GAP2 or Rab18 destabilizes Rab7-positive compartments and perturbs lysosomal biosynthetic transport. Rab3GAP2 and Rab18 are present on autophagosomal and autolysosomal membranes, colocalizing with Vps34 Complex I subunits. Co-immunoprecipitation (GTP-bound Rab18 pull-down with Atg6/Beclin1), genetic epistasis (Atg14/UVRAG overexpression phenocopying Rab3GAP-Rab18 loss), Drosophila mutant model, colocalization studies The FEBS journal Medium 32248620
2020 Rab18 interacts with the ER-resident protein kinectin-1 and controls anterograde kinesin-1-dependent ER transport required for maturation of nascent focal adhesions. Rab18 knockdown reduces focal adhesion size and impairs directional migration in chemotaxis. Rab18 promotes ER-focal adhesion contact formation. siRNA knockdown, live-cell TIRF microscopy of focal adhesions, co-immunoprecipitation of Rab18 with kinectin-1, ER transport assays, chemotaxis assays The Journal of cell biology High 32525992
2020 Rab18 binds to classical swine fever virus (CSFV) NS5A protein; co-immunoprecipitation, GST-pulldown, and confocal microscopy confirm the interaction. Rab18 knockdown reduces CSFV RNA replication and virion assembly, and NS5A is redistributed in Rab18-knockdown cells. Co-immunoprecipitation, GST-pulldown, confocal microscopy, siRNA knockdown, RT-qPCR, IFA for viral protein localization Virulence Medium 32419589
2021 LD-associated Rab18 binds to the C-terminus of perilipin 2 (PLIN2); PLIN2 depletion diminishes LD localization of Rab18. Rab18 also interacts with ACSL3 and promotes ACSL3 LD localization, forming a Rab18-PLIN2-ACSL3 complex. Loss of Rab18 reduces triacylglycerol levels and causes fewer but larger LDs in myoblast cells; overexpression increases TAG and LD number. Co-immunoprecipitation, siRNA knockdown of PLIN2 and ACSL3, Rab18 overexpression/knockdown, TAG quantification, LD morphology analysis in C2C12 myoblast cells Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 33713834
2023 Proximity biotinylation (BioID) identified 28 GEF-dependent RAB18 interactors. Novel interactions with SEC22A, TMCO4, and INPP5B were directly validated. RAB18 interacts with the sterol isomerase EBP and lipid transporter ORP2/OSBPL2. RAB18 loss or dysregulation causes accumulation of the cholesterol precursor lathosterol (EBP product) and impairs de novo cholesterol biosynthesis, implicating RAB18 in sterol mobilization at membrane contact sites. Proximity biotinylation (BioID), validation co-IPs, cholesterol precursor quantification by mass spectrometry in RAB18-null HeLa cells and RAB3GAP1-null patient fibroblasts, de novo cholesterol biosynthesis assays The Journal of biological chemistry High 37774976
2019 Rab18 plays a role upstream of adipose triglyceride lipase (ATGL) in lipolysis; dominant-negative GDP-locked Rab18-S22N causes loss of GFP-ATGL and Arf4-GFP from LD surfaces, similar to brefeldin A treatment targeting GBF1/Arf exchange factors. Arf4-GFP accumulates on Rab18-positive LDs, suggesting Rab18 recruits ATGL via the Arf/GBF1 machinery. Dominant-negative Rab18-S22N expression, GFP-ATGL and Arf4-GFP localization assays, brefeldin A treatment, live-cell imaging Biochemical and biophysical research communications Medium 31610914
2024 2'3'-cGAMP binds Rab18 directly and facilitates GTP loading, thereby activating Rab18. Activated Rab18 promotes FosB transcription to facilitate cell migration. Lovastatin-induced deprenylation of Rab18 abolishes 2'3'-cGAMP recognition and suppresses cell migration, establishing a cGAS/cGAMP/Rab18/FosB signaling axis in cell migration independent of innate immunity. 2'3'-cGAMP interactome/pulldown, GTP loading assays, FosB transcription reporter, Rab18 knockdown/overexpression, migration assays, lovastatin treatment Science advances Medium 39413198
2023 The small GTPase RAB18 recruits the latent CSNCSN7A-CRL3 complex to lipid droplets during adipogenesis. CRL3 is activated by neddylation at LDs, and this is an essential event for LD formation during adipogenesis. Knockdown of CSN7A or RAB18 blocks adipogenesis. Co-immunoprecipitation, siRNA knockdown of RAB18 and CSN7A, adipogenesis assays, neddylation inhibition iScience Medium 37091236
2024 PRRSV-2 infection transcriptionally upregulates RAB18 through RIG-I/MAVS-mediated canonical NF-κB activation. RAB18 promotes chaperone-mediated autophagy (CMA)-mediated lipolysis; during PRRSV-2 infection, enhanced associations are detected between RAB18 and PLIN2, LAMP2A, and HSPA8/HSC70. The C-terminal domain of HSPA8 binds the switch II domain of RAB18, and the CTD of PLIN2 associates with HSPA8, indicating HSPA8 bridges RAB18 and PLIN2 in CMA-mediated lipolysis. shRNA screen, co-immunoprecipitation of RAB18 with PLIN2/LAMP2A/HSPA8, domain mapping by pulldown, NF-κB pathway inhibition, LAMP2A/HSPA8 knockdown with viral yield readout PLoS pathogens Medium 38607975
2025 Rab18 in its GTP-bound state anchors to membranes at basal bodies in Chlamydomonas and recruits the BBSome as an effector to facilitate BBSome diffusion through the transition zone for ciliary entry, thereby maintaining ciliary homeostasis of signaling proteins (including phospholipase D). Localization studies in Chlamydomonas, dominant GTPase state mutants, BBSome co-localization and functional ciliary entry assays bioRxivpreprint Low bio_10.1101_2025.02.04.636545

Source papers

Stage 0 corpus · 66 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Rab18 localizes to lipid droplets and induces their close apposition to the endoplasmic reticulum-derived membrane. Journal of cell science 313 15914536
2005 Regulated localization of Rab18 to lipid droplets: effects of lipolytic stimulation and inhibition of lipid droplet catabolism. The Journal of biological chemistry 248 16207721
2018 Rab18 promotes lipid droplet (LD) growth by tethering the ER to LDs through SNARE and NRZ interactions. The Journal of cell biology 195 29367353
2011 Loss-of-function mutations in RAB18 cause Warburg micro syndrome. American journal of human genetics 147 21473985
2008 Rab18 and Rab43 have key roles in ER-Golgi trafficking. Journal of cell science 137 18664496
2013 Rab18 binds to hepatitis C virus NS5A and promotes interaction between sites of viral replication and lipid droplets. PLoS pathogens 118 23935497
2014 Rab18 and a Rab18 GEF complex are required for normal ER structure. The Journal of cell biology 115 24891604
2014 Rab18 facilitates dengue virus infection by targeting fatty acid synthase to sites of viral replication. Journal of virology 111 24696471
2011 Rab18 dynamics in adipocytes in relation to lipogenesis, lipolysis and obesity. PloS one 111 21829560
2013 Mutation spectrum in RAB3GAP1, RAB3GAP2, and RAB18 and genotype-phenotype correlations in warburg micro syndrome and Martsolf syndrome. Human mutation 110 23420520
2014 MicroRNA-30b/c inhibits non-small cell lung cancer cell proliferation by targeting Rab18. BMC cancer 101 25249344
2016 COPI-TRAPPII activates Rab18 and regulates its lipid droplet association. The EMBO journal 81 28003315
2013 Hepatitis B virus X protein upregulates oncogene Rab18 to result in the dysregulation of lipogenesis and proliferation of hepatoma cells. Carcinogenesis 80 23471881
2016 MiR-455-5p acts as a novel tumor suppressor in gastric cancer by down-regulating RAB18. Gene 49 27451075
2014 Rab18 is required for viral assembly of hepatitis C virus through trafficking of the core protein to lipid droplets. Virology 49 24997429
2007 Rab18 inhibits secretory activity in neuroendocrine cells by interacting with secretory granules. Traffic (Copenhagen, Denmark) 45 17488286
2021 Rab18 binds PLIN2 and ACSL3 to mediate lipid droplet dynamics. Biochimica et biophysica acta. Molecular and cell biology of lipids 43 33713834
2017 The RAB GTPase RAB18 modulates macroautophagy and proteostasis. Biochemical and biophysical research communications 43 28342870
2015 Liver X receptors balance lipid stores in hepatic stellate cells through Rab18, a retinoid responsive lipid droplet protein. Hepatology (Baltimore, Md.) 41 25482505
2015 Warburg Micro syndrome is caused by RAB18 deficiency or dysregulation. Open biology 41 26063829
2019 Rab18: new insights into the function of an essential protein. Cellular and molecular life sciences : CMLS 37 30830238
2019 RAB18 Loss Interferes With Lipid Droplet Catabolism and Provokes Autophagy Network Adaptations. Journal of molecular biology 36 31874152
2017 Identification of Rab18 as an Essential Host Factor for BK Polyomavirus Infection Using a Whole-Genome RNA Interference Screen. mSphere 35 28815213
2018 Rab18 is not necessary for lipid droplet biogenesis or turnover in human mammary carcinoma cells. Molecular biology of the cell 32 29949452
2019 Rab18 Collaborates with Rab7 to Modulate Lysosomal and Autophagy Activities in the Nervous System: an Overlapping Mechanism for Warburg Micro Syndrome and Charcot-Marie-Tooth Neuropathy Type 2B. Molecular neurobiology 27 30721447
2016 RAB18, a protein associated with Warburg Micro syndrome, controls neuronal migration in the developing cerebral cortex. Molecular brain 27 26879639
2016 Acute accumulation of free cholesterol induces the degradation of perilipin 2 and Rab18-dependent fusion of ER and lipid droplets in cultured human hepatocytes. Molecular biology of the cell 24 27582390
2019 miR-145-5p Acts as a Novel Tumor Suppressor in Hepatocellular Carcinoma Through Targeting RAB18. Technology in cancer research & treatment 23 31106707
2012 RAB3GAP1, RAB3GAP2 and RAB18: disease genes in Micro and Martsolf syndromes. Biochemical Society transactions 23 23176487
2011 Rab proteins and the secretory pathway: the case of rab18 in neuroendocrine cells. Frontiers in endocrinology 22 22649356
2008 Rab18 is reduced in pituitary tumors causing acromegaly and its overexpression reverts growth hormone hypersecretion. The Journal of clinical endocrinology and metabolism 21 18349058
2020 The Warburg Micro Syndrome-associated Rab3GAP-Rab18 module promotes autolysosome maturation through the Vps34 Complex I. The FEBS journal 20 32248620
2024 Porcine reproductive and respiratory syndrome virus 2 hijacks CMA-mediated lipolysis through upregulation of small GTPase RAB18. PLoS pathogens 19 38607975
2020 Rab18 binds to classical swine fever virus NS5A and mediates viral replication and assembly in swine umbilical vein endothelial cells. Virulence 18 32419589
2020 Rab18 regulates focal adhesion dynamics by interacting with kinectin-1 at the endoplasmic reticulum. The Journal of cell biology 18 32525992
2000 Isolation and characterisation of the human rab18 gene after stimulation of endothelial cells with histamine. FEBS letters 17 10648831
1997 Rab17 and rab18, small GTPases with specificity for polarized epithelial cells: genetic mapping in the mouse. Genomics 17 9367688
2025 Diallyl Trisulfide From Garlic Regulates RAB18 Phase Separation to Inhibit Lipophagy and Induce Cuproptosis in Hepatic Stellate Cells for Antifibrotic Effects. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 16 40213908
2018 Rab18 overexpression promotes proliferation and chemoresistance through regulation of mitochondrial function in human gastric cancer. OncoTargets and therapy 16 30464528
2020 Rab18 Regulates Proliferation, Invasion and Cisplatin Sensitivity Through STAT3 Signaling in Head and Neck Squamous Cell Carcinoma. OncoTargets and therapy 11 32494165
2012 Nutritional, hormonal, and depot-dependent regulation of the expression of the small GTPase Rab18 in rodent adipose tissue. Journal of molecular endocrinology 11 23093555
2024 Leishmania highjack host lipid body for its proliferation in macrophages by overexpressing host Rab18 and TRAPPC9 by downregulating miR-1914-3p expression. PLoS pathogens 10 38412149
2023 Latent CSN-CRL complexes are crucial for curcumin-induced apoptosis and recruited during adipogenesis to lipid droplets via small GTPase RAB18. iScience 9 37091236
2019 RAB18 modulates autophagy in human stellate cells. Journal of clinical lipidology 9 31563421
2015 ENU mutagenesis identifies mice modeling Warburg Micro Syndrome with sensory axon degeneration caused by a deletion in Rab18. Experimental neurology 9 25779931
2023 Comparative proximity biotinylation implicates the small GTPase RAB18 in sterol mobilization and biosynthesis. The Journal of biological chemistry 8 37774976
2019 RAB18 promotes proliferation and metastasis in hepatocellular carcinoma. American journal of translational research 8 30899400
2014 Bacterial-induced expression of RAB18 protein in Orzya sativa salinity stress and insights into molecular interaction with GTP ligand. Journal of molecular recognition : JMR 8 25042706
2005 Analysis of Rab18 and a new golgin in the secretory pathway. Annals of the New York Academy of Sciences 8 15891017
2024 Rab18 maintains homeostasis of subcutaneous adipose tissue to prevent obesity-induced metabolic disorders. Science China. Life sciences 7 38523235
2017 TRAPPing Rab18 in lipid droplets. The EMBO journal 7 28130247
2024 2'3'-cGAMP interactome identifies 2'3'-cGAMP/Rab18/FosB signaling in cell migration control independent of innate immunity. Science advances 6 39413198
2022 RAB18 is a key regulator of GalNAc-conjugated siRNA-induced silencing in Hep3B cells. Molecular therapy. Nucleic acids 6 35505960
2021 miR-455 Inhibits the Viability and Invasion by Targeting RAB18 in Hepatocellular Carcinoma. Journal of oncology 4 34135963
2019 Rab18 regulates lipolysis via Arf/GBF1 and adipose triglyceride lipase. Biochemical and biophysical research communications 4 31610914
2014 The association of RAB18 gene polymorphism (rs3765133) with cerebellar volume in healthy adults. Cerebellum (London, England) 4 24996981
2024 Effect of Rab18 on liver injury and lipid accumulation by regulating perilipin 2 and peroxisome proliferator-activated receptor gamma in non-alcoholic fatty liver disease. Journal of gastroenterology and hepatology 3 39030773
2005 Cloning and characterization of a novel splice variant of human Rab18 gene (RAB18). DNA sequence : the journal of DNA sequencing and mapping 2 16147880
2025 RAB18 deficiency disrupts lipid metabolism and autophagy in mice. Biochemical and biophysical research communications 1 40157288
2025 The Rab18/Ras/ERK/FosB/MMP3 Signaling Pathway Mediates Cell Migration Regulation by 2'3'-cGAMP. International journal of molecular sciences 1 40565221
2024 The small GTPase RAB-18 is involved in regulating development/diapause by recruiting the intestinal cholesterol transporter NCR-1 onto the apical side in Caenorhabditis elegans. Biochemical and biophysical research communications 1 39232459
2026 Unconventional Secretion of Angiogenic Sonic Hedgehog-Containing Extra-Large Extracellular Vesicles is Driven by PI3K-Rab18-GDP Signalling. Journal of extracellular biology 0 41614083
2025 Curcumol ameliorates high-fat diet-induced hepatic fibrosis via dual regulation of FXR-CREB and Rab18-mediated hepatic stellate cell lipophagy. Biochimica et biophysica acta. Molecular and cell biology of lipids 0 41390076
2025 RAB18 is upregulated in colorectal cancer and promotes tumor progression. Pathology, research and practice 0 41468642
2024 RAB18 regulates extrahepatic siRNA-mediated gene silencing efficacy. Molecular therapy. Nucleic acids 0 39380712
2015 Molecular cloning, sequence characterization and expression pattern of Rab18 gene from watermelon (Citrullus lanatus). Biotechnology, biotechnological equipment 0 26019638

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