Affinage

ARL13B

ADP-ribosylation factor-like protein 13B · UniProt Q3SXY8

Length
428 aa
Mass
48.6 kDa
Annotated
2026-06-09
65 papers in source corpus 37 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ARL13B is an atypical, ciliary-membrane-anchored small GTPase of the ARF/ARL family that organizes the protein composition and signaling output of the primary cilium (PMID:18674751, PMID:20231383, PMID:24168557). Its structure carries an incomplete active site that abolishes intrinsic GTP hydrolysis, and biochemically it acts principally as a guanine nucleotide exchange factor (GEF) for ARL3, generating a spatially restricted ARL3·GTP compartment within cilia that drives release of lipidated ciliary cargo (PMID:24168557, PMID:26551564, PMID:28487361). Membrane targeting depends on N-terminal palmitoylation—which also stabilizes the protein—and a C-terminal RVEP/RVVP ciliary-targeting sequence, with ciliary delivery mediated by TULP3/IFT-A and by a Rab8-GDP/TNPO1 import system; AHI1 promotes its ciliary recruitment and proteasomal stability (PMID:28848045, PMID:36652335, PMID:36907439, PMID:24339792, PMID:31391239). Within cilia, ARL13B controls trafficking and dynamic distribution of signaling receptors including Smoothened and GPR161, promotes ciliary targeting of INPP5E, binds tubulin through its G-domain to anchor membrane proteins along the axoneme, and directs axoneme polyglutamylation via a RAB11-FIP5–dependent import of TTLL5/6 glutamylases—together enabling Sonic hedgehog signal transduction (PMID:21976698, PMID:27927754, PMID:23150559, PMID:30120249, PMID:40707593). Engineered cilia-excluded (V358A) and GEF-deficient (R79Q) alleles separate these activities, showing that Shh regulation is largely extraciliary while ciliary ARL13B and its ARL3 GEF activity are required for Pkd1-dependent renal cystogenesis, and ciliary ARL13B governs body-weight homeostasis and photoreceptor outer-segment function (PMID:32129762, PMID:37577625, PMID:40721319, PMID:30573647). Beyond cilia ARL13B operates in endocytic recycling and in actin- and integrin-dependent cell migration through interactions with Myh9 and β3-integrin (PMID:23223633, PMID:24777479, PMID:31569511). Missense mutations that disrupt the ARL13B–INPP5E interaction or impair ARL3 GEF activity cause Joubert syndrome (PMID:23150559, PMID:29255182).

Mechanistic history

Synthesis pass · year-by-year structured walk · 30 steps
  1. 2008 High

    Established that ARL13B is a bona fide ciliary protein whose function is evolutionarily conserved and disease-relevant, anchoring all subsequent mechanistic work.

    Evidence Zebrafish rescue with wild-type versus patient-mutant ARL13B and immunolocalization in murine neurons

    PMID:18674751

    Open questions at the time
    • Did not define the molecular activity of ARL13B
    • No partners or substrates identified
  2. 2010 High

    Defined how ARL13B reaches and acts at the cilium, linking membrane anchoring to maintenance of ciliary ultrastructure, transmembrane protein content, and IFT stability.

    Evidence C. elegans genetics, IFT motility assays, and epistasis with ciliogenic/IFT genes

    PMID:20231383

    Open questions at the time
    • Palmitoylation inferred from motifs, not yet demonstrated biochemically
    • Direct IFT-complex partners not yet mapped
  3. 2009 High

    Showed that correct ciliary localization is necessary for in vivo function, framing ARL13B targeting as a mechanistic requirement rather than a passive marker.

    Evidence Systematic deletion/point-mutant rescue in arl13b/scorpion zebrafish

    PMID:19906870

    Open questions at the time
    • Targeting sequences not yet molecularly resolved
    • Did not separate ciliary from extraciliary roles
  4. 2011 High

    Connected ARL13B to Sonic hedgehog signaling by showing it controls dynamic Smoothened distribution in cilia.

    Evidence Smo immunofluorescence in Arl13b-null versus wild-type cilia under Shh stimulation

    PMID:21976698

    Open questions at the time
    • Mechanism of Smo control (direct vs indirect) not resolved
    • Did not address other Hh-pathway receptors
  5. 2012 High

    Identified ARL13B as a hub for ciliary lipid-signaling by demonstrating a direct INPP5E interaction required for INPP5E ciliary targeting, with Joubert mutations disrupting this link.

    Evidence Co-IP/binding assays, ciliary localization, and patient mutation analysis defining an ARL13B-INPP5E-PDE6D-CEP164 network

    PMID:23150559

    Open questions at the time
    • GEF activity toward ARL3 not yet established
    • Mechanism coupling INPP5E import to downstream signaling unresolved
  6. 2012 High

    Extended ARL13B function to neuronal cilia, showing it controls guidance-receptor dynamics needed for interneuron migration and placement.

    Evidence Conditional knockout mice, live imaging of interneuronal cilia, guidance-receptor immunofluorescence

    PMID:23153492

    Open questions at the time
    • Specific receptors mechanistically regulated not fully defined
    • Cilia-dependence versus extraciliary contribution not separated
  7. 2012 Medium

    Revealed an extraciliary role in endocytic recycling, indicating ARL13B function is not confined to the cilium.

    Evidence shRNA knockdown, CD1a surface/recycling flow cytometry, endosome morphology, colocalization with Arf6/Rab22a

    PMID:23223633

    Open questions at the time
    • Direct effectors in recycling pathway not identified
    • Single lab; mechanism of endosome clustering unresolved
  8. 2012 Medium

    Placed ARL13B within neural-tube patterning logic, showing it uncouples Gli activator/repressor balance during a defined critical period and acts non-autonomously on BMP signaling.

    Evidence Temporal/conditional Arl13b deletion, Gli3 epistasis, in situ hybridization for BMP/Wnt components

    PMID:21539826 PMID:23014696

    Open questions at the time
    • Molecular mechanism linking ARL13B to GliA/GliR ratio unresolved
    • Non-autonomous BMP effect mechanistically indirect
  9. 2013 High

    Defined the subciliary compartmentalization of ARL13B and its requirement for an RVVP motif and membrane anchoring, while mapping IFT-B associations and IFT-like motility.

    Evidence C. elegans genetics across >20 mutants, in vivo FRAP, and mass-spectrometry interactome (IFT46, IFT74)

    PMID:24339792

    Open questions at the time
    • Functional importance of IFT-B binding versus localization not separated here
    • Human relevance of compartment boundaries not tested
  10. 2014 High

    Established a structural basis for ARL13B's atypical biochemistry, showing an incomplete active site explains absent intrinsic hydrolysis and that patient mutations destabilize key conformational residues.

    Evidence X-ray crystallography of Chlamydomonas Arl13B with biochemical GTPase assays and mutant analysis

    PMID:24168557

    Open questions at the time
    • No human full-length structure
    • Catalytic partner (GEF target) not yet identified structurally
  11. 2014 High

    Showed ARL13B directly binds tubulin via its G-domain independently of GTPase activity to anchor ciliary membrane proteins uniformly along the axoneme.

    Evidence Co-IP, in vitro binding, structure-function mutagenesis, and rescue of null MEF ciliogenesis defects

    PMID:29592971

    Open questions at the time
    • Tubulin-binding interface not mapped at residue level
    • How anchoring couples to signaling output unresolved
  12. 2014 Medium

    Linked ARL13B GTPase activity to ciliary membrane extension and placed it downstream of ciliogenic transcription factors FoxJ1/Rfx.

    Evidence Zebrafish and mammalian overexpression/loss-of-function with GTPase-dead variants

    PMID:25448689

    Open questions at the time
    • Mechanism of membrane protrusion not defined
    • Single lab; relationship to GEF activity unaddressed
  13. 2014 Medium

    Uncovered extraciliary migration functions through GTP-dependent exocyst binding and a Myh9-dependent role in circular dorsal ruffles.

    Evidence GTP/GDP pulldowns, direct binding to Sec8/Sec5, Co-IP with Myh9, RNAi, and zebrafish neural-crest migration assays

    PMID:24777479 PMID:26582389

    Open questions at the time
    • Whether exocyst binding operates at cilia or elsewhere not resolved
    • Direct versus indirect Myh9 effect on migration unresolved
  14. 2015 High

    Defined ARL13B's central enzymatic identity as the GEF for ARL3, establishing that it spatially restricts ARL3·GTP to cilia to license cargo release, with Joubert mutations impairing this activity.

    Evidence In vitro GEF reconstitution, structural analysis, mammalian overexpression, and patient mutation testing

    PMID:26551564

    Open questions at the time
    • Full set of lipidated cargoes released downstream not enumerated
    • In vivo requirement of GEF activity not yet tested by knock-in
  15. 2017 High

    Consolidated the atypical GTPase/GEF biochemistry with purified protein and identified casein kinase 2 phosphorylation as a regulatory modification.

    Evidence Recombinant murine Arl13b nucleotide-binding, GTPase, and GEF assays plus mutation characterization

    PMID:28487361

    Open questions at the time
    • Functional consequence of CK2 phosphorylation not defined
    • Regulation of GEF activity in vivo unresolved
  16. 2017 High

    Established palmitoylation as the in vivo determinant of ciliary trafficking, stability, and function, distinguishing localization from function.

    Evidence Biochemical palmitoylation assays in mouse kidney, myristoylation substitution, stability and rescue experiments

    PMID:28848045

    Open questions at the time
    • Palmitoyltransferase/thioesterase enzymes not identified
    • How palmitoylation supports function beyond localization unresolved
  17. 2016 High

    Resolved the order of trafficking determinants, showing ciliary localization depends on the RVEP CTS and that INPP5E binding—not IFT-B binding—drives IFT-A-mediated retrograde GPR161 exit.

    Evidence Visible immunoprecipitation, ARL13B-knockout cells, and rescue with interaction-specific mutants

    PMID:27927754

    Open questions at the time
    • Precise step at which retrograde exit fails not defined
    • Mechanistic coupling of INPP5E to IFT-A machinery unresolved
  18. 2017 Medium

    Implicated ARL13B-Smo interaction in cancer Hedgehog signaling via control of Smo stability and trafficking.

    Evidence Co-IP, trafficking assays, tumor proliferation/invasion assays, and in vivo gastric cancer models

    PMID:28611043

    Open questions at the time
    • Direct versus indirect Smo binding not biochemically resolved
    • Single disease context
  19. 2018 High

    Connected ARL13B to axoneme tubulin polyglutamylation through RAB11-FIP5-dependent import of TTLL5/6 glutamylases, mechanistically linking it to sensory receptor anchoring.

    Evidence Co-IP for ARL13B-FIP5, TTLL5/6 localization, and CCP5-depletion rescue of hypoglutamylation

    PMID:30120249

    Open questions at the time
    • Whether GEF or GTPase activity is required for this trafficking unresolved
    • Direct glutamylase recruitment mechanism not fully defined
  20. 2018 Medium

    Identified TULP3 as a trafficking adaptor that delivers ARL13B (and INPP5E) to cilia via IFT-A binding, with TUB redundancy.

    Evidence TULP3-knockout RPE1 cells rescued with wild-type and IFT-A-binding-deficient TULP3

    PMID:30583862

    Open questions at the time
    • Relationship to palmitoylation-dependent targeting not resolved here
    • Single lab
  21. 2018 High

    Established ARL13B as essential across retinogenesis stages and for photoreceptor outer-segment morphogenesis and protein trafficking.

    Evidence Pan-retina and inducible conditional knockout mice with ERG, immunofluorescence, and electron microscopy

    PMID:30573647

    Open questions at the time
    • Ciliary versus GEF contributions not separated in this study
    • Specific cargo-trafficking step disrupted not fully defined
  22. 2018 High

    Tied loss of ARL3 GEF activity directly to Joubert syndrome through a patient variant that selectively abolishes GEF function while preserving GTPase and rescue capacity.

    Evidence Whole-exome sequencing plus GEF, cilia-length, and Shh rescue assays for the Gly75Arg variant

    PMID:29255182

    Open questions at the time
    • Which downstream cargo defect causes disease not pinpointed
    • Genotype-phenotype breadth across patients not addressed
  23. 2019 High

    Demonstrated a cilia-independent ARL13B function in Shh-mediated axon guidance, with a cilia-excluded variant sufficient for guidance.

    Evidence Conditional knockout, in vitro axon guidance assays, and cilia-excluded variant rescue

    PMID:31825820

    Open questions at the time
    • Molecular effectors of axonal ARL13B not identified
    • How extraciliary ARL13B transduces Shh locally unresolved
  24. 2019 Medium

    Identified AHI1 as a regulator of ARL13B ciliary recruitment and proteasomal stability, affecting Shh signaling and motility.

    Evidence Ahi1-knockout MEFs with localization, proteasome-inhibition stability assays, Shh readouts, and migration assays

    PMID:31391239

    Open questions at the time
    • Whether AHI1 acts directly on ARL13B unresolved
    • E3 ligase controlling degradation not identified
  25. 2019 Medium

    Defined an extraciliary migration mechanism through focal-adhesion localization and β3-integrin interaction controlling surface integrin and adhesion dynamics.

    Evidence siRNA, focal-adhesion immunofluorescence, Co-IP with β3-integrin, surface flow cytometry, and orthotopic breast cancer model

    PMID:31569511

    Open questions at the time
    • Nucleotide-state dependence of integrin binding not defined
    • Single lab
  26. 2020 High

    Genetically uncoupled ciliary from extraciliary ARL13B, showing the V358A cilia-excluded allele supports normal Shh signaling despite short cilia lacking ARL3 and INPP5E—establishing Shh regulation as primarily extraciliary.

    Evidence V358A knock-in mouse with Shh readouts and retrograde-transport blockade experiments

    PMID:32129762

    Open questions at the time
    • Where extraciliary Shh transduction occurs spatially not resolved
    • Mechanism of short cilia in V358A not fully defined
  27. 2022 Medium

    Linked ARL13B to vascular signaling via VEGFR2 interaction and localization control, and to PAK2-driven ciliogenesis in brain endothelium.

    Evidence GST-pulldown, Co-IP, luciferase reporters, endothelial mouse models, and zebrafish pak2a rescue

    PMID:35700757 PMID:36322624

    Open questions at the time
    • Direct versus indirect VEGFR2 regulation not fully resolved
    • Single lab per context
  28. 2023 High

    Mapped the molecular logic of ARL13B ciliary import, defining a TULP3-tubby/N-terminal amphipathic helix route and a Rab8-GDP/TNPO1 system recognizing the RVEP CTS.

    Evidence Domain mapping with knockout rescue, purified-protein pulldowns, TurboID proximity labeling, and RNAi

    PMID:36652335 PMID:36907439

    Open questions at the time
    • Hand-off between palmitoylation, TULP3, and Rab8/TNPO1 routes not integrated
    • Regulation of Rab8 nucleotide state in this context unresolved
  29. 2025 High

    Dissected in vivo physiological requirements using V358A and R79Q alleles, showing ciliary ARL13B is required for body-weight homeostasis (GEF-independent) and that ciliary localization plus GEF activity are required for Pkd1-dependent renal cystogenesis.

    Evidence Knock-in mouse models with inducible re-expression, metabolic phenotyping, and Pkd1-cross cystogenesis readouts

    PMID:37577625

    Open questions at the time
    • Cyst study is a preprint without listed PMID
    • Downstream ciliary signal mediating weight control not identified
  30. 2025 Medium

    Further separated ciliary from GEF activity in photoreceptors and revealed roles in spermatogenesis and absolute ciliogenesis, while connecting splicing regulation to ARL13B isoform function.

    Evidence V358A/R79Q knock-in ERG/EM analyses, CRISPR knockouts, rescue breeding, and PRPF8-dependent splicing with zebrafish isoform overexpression

    PMID:40501629 PMID:40707593 PMID:40721319 PMID:40916698

    Open questions at the time
    • Mechanism of spermatogenesis role undefined
    • Functional role of exon-9-lacking isoform partly preprint-stage

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ARL13B's distinct biochemical activities (ARL3 GEF, tubulin binding, atypical GTP binding) are individually deployed across its many ciliary and extraciliary functions, and which downstream effectors transduce each, remains incompletely resolved.
  • No unified model linking nucleotide state to specific cargo decisions
  • Extraciliary Shh transduction mechanism unknown
  • Enzymes controlling palmitoylation cycle and degradation unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0003924 GTPase activity 2 GO:0098772 molecular function regulator activity 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005929 cilium 6 GO:0005886 plasma membrane 3 GO:0005856 cytoskeleton 2 GO:0005768 endosome 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-9609507 Protein localization 4 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1643685 Disease 2
Partners
ARL3IFT46INPP5EMYH9RAB8SMOTNPO1TULP3

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 ARL13B protein localizes to cilia in primary neurons and is required for cilia function; overexpression of human wild-type but not patient mutant ARL13B rescued the Arl13b scorpion zebrafish mutant, establishing evolutionary conservation of its ciliary role. Zebrafish rescue experiments, immunofluorescence localization in murine neurons American journal of human genetics High 18674751
2010 C. elegans ARL-13/Arl13b localizes to proximal ciliary membranes via palmitoylation modification motifs; loss-of-function causes defects in cilium morphology/ultrastructure, abnormal accumulation of ciliary transmembrane proteins, elevated PKD-2 ciliary abundance, and destabilized anterograde intraflagellar transport (IFT). Genetic interaction with other ciliogenic/IFT genes confirmed its role in anterograde IFT stability. C. elegans genetics, fluorescence microscopy, IFT motility assays, genetic epistasis The Journal of cell biology High 20231383
2009 Multiple regions of Arl13b are required for its ciliary localization, and ciliary localization is essential for in vivo function; ciliary-localization-defective mutants cannot rescue arl13b/scorpion zebrafish phenotypes. Zebrafish rescue experiments with deletion and point mutants Development (Cambridge, England) High 19906870
2011 Arl13b regulates the ciliary entry and distribution of Smoothened (Smo); in Arl13b-null cilia, Smo is enriched regardless of Shh pathway stimulation, indicating Arl13b controls the dynamic localization of Smo within the cilium and thereby regulates Sonic hedgehog signaling. Mouse mutant analysis, immunofluorescence of Smo localization in Arl13b-null vs. wild-type cilia in vitro Molecular biology of the cell High 21976698
2012 ARL13B physically interacts with INPP5E and is required for ciliary targeting of INPP5E; JBTS-causing missense mutations in ARL13B disrupt the ARL13B-INPP5E interaction. ARL13B, INPP5E, PDE6D, and CEP164 form a distinct functional network for INPP5E ciliary targeting. Protein-protein interaction studies (Co-IP, binding assays), cell-based localization, patient mutation analysis Proceedings of the National Academy of Sciences of the United States of America High 23150559
2012 Arl13b is required in primary cilia for proper migration and placement of interneurons in the developing cerebral cortex; guidance cue receptors essential for interneuronal migration localize to interneuronal primary cilia, but their concentration and dynamics are altered in the absence of Arl13b. Live imaging of interneuronal cilia, mouse conditional knockout, immunofluorescence of guidance receptors Developmental cell High 23153492
2012 Arl13b is required for endocytic recycling traffic; silencing Arl13b reduces CD1a surface expression and delays CD1a recycling, causes clustering of early endosomes and accumulation of endocytic cargo. Arl13b colocalizes with Arf6 and Rab22a (endocytic recycling markers) and interacts with the actin cytoskeleton. shRNA knockdown screen, flow cytometry for CD1a surface expression, fluorescence colocalization, endosome morphology analysis Proceedings of the National Academy of Sciences of the United States of America Medium 23223633
2013 ARL13B/ARL-13 is restricted to an Inv-like subciliary membrane compartment; compartmentalization requires a C-terminal RVVP motif and membrane anchoring. IFT-A/B, IFT-dynein and BBS genes prevent ARL-13 periciliary membrane accumulation; MKS/NPHP modules additionally inhibit ARL-13 at the transition zone. ARL-13 undergoes IFT-like motility and human ARL13B has functional associations with IFT-B complexes via IFT46 and IFT74 interactions. C. elegans genetics (>20 mutants), quantitative fluorescence imaging, in vivo FRAP, quantitative protein complex analysis (mass spectrometry) PLoS genetics High 24339792
2014 ARL13B directly interacts with tubulin via its G-domain independently of GTPase activity; this interaction is required for ARL13B to anchor ciliary membrane proteins (Smo, SSTR3) uniformly along the cilium. Mutants lacking the tubulin-binding G-domain fail to rescue ciliogenesis defects of null MEFs and cause uneven distribution of membrane proteins. Co-immunoprecipitation, in vitro binding assays, mutagenesis, immunofluorescence in MEFs Journal of cell science High 29592971
2014 Overexpression of Arl13b increases ciliary length by inducing protrusion of the ciliary membrane followed by axonemal extension; GTPase activity of Arl13b is essential for this membrane extension. Arl13b is induced by ciliogenic transcription factors FoxJ1 and Rfx and acts downstream of them to regulate ciliary length. Zebrafish overexpression and loss-of-function, mammalian cell overexpression, mutant analysis including GTPase-dead variants Developmental biology Medium 25448689
2014 Arl13b localizes to circular dorsal ruffles (CDRs) and interacts with non-muscle myosin heavy chain IIA (Myh9) as an effector; both proteins are required for CDR formation and cell migration. Arl13b silencing impairs neural crest cell migration in zebrafish. Co-immunoprecipitation, RNAi knockdown, fluorescence microscopy of CDRs, zebrafish neural crest migration assay Journal of cell science Medium 24777479
2014 Crystal structure of Chlamydomonas reinhardtii Arl13B reveals an incomplete active site accounting for absence of intrinsic GTP hydrolysis. Patient mutations R79Q and R200C destabilize important intramolecular interactions; Arg79 is crucial for the GDP/GTP conformational change typical of Arf/Arl proteins. X-ray crystallography, biochemical GTPase assays, structural analysis of patient mutants The Biochemical journal High 24168557
2015 Arl13B is the guanine nucleotide exchange factor (GEF) for Arl3; GEF activity is mediated by the G-domain plus an additional C-terminal helix, with switch regions of Arl13B involved in interaction with Arl3. Overexpression of Arl13B increases Arl3·GTP levels in mammalian cells, and Joubert syndrome patient mutations impair GEF activity. This spatial restriction of Arl3 activation to cilia generates an Arl3·GTP compartment for ciliary cargo release. In vitro GEF assay, structural analysis, overexpression in mammalian cells, patient mutation analysis eLife High 26551564
2015 The GTP-bound form of Arl13b preferentially binds exocyst subunits Sec8, Exo70, and Sec5 (consistent with the exocyst being an effector); Arl13b binds directly to Sec8 and Sec5. Genetic interaction between arl13b and exocyst subunit sec10 in zebrafish shows synergistic cilia-dependent phenotypes, and Arl13b and the exocyst function in the same ciliogenesis pathway. Pulldown assays (GTP vs. GDP-bound Arl13b), direct binding assays, zebrafish morphant genetic interaction, conditional mouse knockout Molecular biology of the cell High 26582389
2016 ARL13B interacts with the IFT46-IFT56 dimer of the IFT-B complex; however, ciliary localization of ARL13B is independent of IFT-B interaction but dependent on the C-terminal RVEP ciliary-targeting sequence. In ARL13B-knockout cells, IFT-A and IFT-B complexes accumulate at ciliary tips and GPR161 cannot exit cilia in response to Smoothened agonist (retrograde exit defect). This abnormal phenotype is rescued by wild-type ARL13B and by an IFT-B-interaction-defective mutant, but not by INPP5E-binding-defective or ciliary-localization-defective mutants, indicating ARL13B regulates IFT-A-mediated retrograde protein trafficking through its interaction with INPP5E. Visible immunoprecipitation assay, ARL13B knockout cells, immunofluorescence, rescue with mutants Journal of cell science High 27927754
2017 Purified recombinant murine Arl13b is biochemically atypical: it binds GTP with lower intrinsic GTPase activity and functions as a GEF for ARL3. Three human Joubert syndrome missense mutations were biochemically characterized. Murine Arl13b is also a substrate for casein kinase 2 phosphorylation. In vitro biochemical assays (nucleotide binding, intrinsic and GAP-stimulated GTPase, GEF activity), recombinant protein purification, patient mutation analysis The Journal of biological chemistry High 28487361
2017 ARL13B palmitoylation occurs in vivo (mouse kidneys) and is required for trafficking to cilia and for ARL13B function within cilia; palmitoylation dramatically increases ARL13B protein stability. Myristoylation can substitute for palmitoylation in ciliary localization but not ciliary function. Blockade of depalmitoylation slows ARL13B degradation during cilia resorption. Biochemical palmitoylation assays, cellular localization studies, in vivo mouse kidney experiments, stability assays, cilia rescue experiments The Journal of biological chemistry High 28848045
2017 Arl13b interacts with Smoothened (Smo) and regulates Smo stability, trafficking, and ciliary localization, which are crucial for Hedgehog signaling in gastric cancer. Co-immunoprecipitation, cell-based trafficking assays, proliferation/migration/invasion assays, in vivo tumor models Cancer research Medium 28611043
2017 A novel ARL13B variant (Gly75Arg) causes Joubert syndrome with a marked loss of ARL3 GEF activity while retaining GTPase activity and cilia/Shh-rescue function, establishing a direct correlation between ARL13B's ARL3 GEF activity loss and Joubert syndrome. Whole-exome sequencing, GEF activity assays, cilia length rescue, Shh signaling rescue in null cells European journal of human genetics : EJHG High 29255182
2018 ARL13B controls axoneme polyglutamylation by interacting with RAB11 effector FIP5 to promote ciliary import of glutamylases TTLL5 and TTLL6. Hypoglutamylation caused by ARL13B deficiency impairs ciliary signaling by disrupting sensory receptor anchoring and signaling molecule trafficking, and can be rescued by depletion of deglutamylase CCP5. Co-immunoprecipitation (ARL13B-FIP5 interaction), immunofluorescence of TTLL5/6 localization, CCP5 depletion rescue, cilia signaling assays Nature communications High 30120249
2018 TULP3 is required for ciliary localization of membrane-associated proteins ARL13B and INPP5E; this function requires TULP3's ability to bind IFT-A. TUB (another tubby family member) can substitute for TULP3 in rescuing ciliary localization of ARL13B, indicating functional redundancy. TULP3-knockout RPE1 cells, immunofluorescence, rescue with wild-type and IFT-A-binding-deficient TULP3 mutants Biochemical and biophysical research communications Medium 30583862
2018 ARL13B is required at multiple stages of retinogenesis including early retinal progenitor proliferation, photoreceptor cilia development, and outer segment disc morphogenesis. Loss of ARL13B in adult photoreceptors causes mislocalization of rhodopsin, prenylated PDE6, and IFT88, and loss of photoresponse. Conditional knockout mouse models (Six3-Cre pan-retina and Pde6g-CreERT2 inducible), ERG, immunofluorescence, electron microscopy The Journal of neuroscience High 30573647
2019 Arl13b functions outside primary cilia in Shh-mediated axon guidance; Arl13b protein is detected in axons and growth cones, and a cilia-localization-deficient Arl13b variant is sufficient to mediate Shh-dependent commissural axon guidance both in vitro and in vivo. In vivo conditional knockout, in vitro axon guidance assays, immunolocalization in axons/growth cones, cilia-excluded variant rescue Cell reports High 31825820
2019 AHI1 promotes Arl13b ciliary recruitment and regulates Arl13b stability via the proteasome; loss of Ahi1 reduces ciliary membrane localization of Arl13b, decreases non-membrane-associated Arl13b stability, reduces Shh signaling, and causes defects in cell motility. Ahi1-knockout MEFs, immunofluorescence, stability assays with proteasome inhibition, Shh signaling readouts, migration assays Journal of cell science Medium 31391239
2019 Arl13b localizes to focal adhesions in breast cancer cells and interacts with β3-integrin; Arl13b silencing increases β3-integrin cell surface levels and FA size while inhibiting integrin-mediated signaling, revealing a mechanism for Arl13b in regulating cell migration and invasion. siRNA knockdown, immunofluorescence localization to focal adhesions, Co-immunoprecipitation with β3-integrin, flow cytometry for surface integrin, in vitro migration/invasion assays, in vivo mouse orthotopic model Cancers Medium 31569511
2020 ARL13B's role within cilia can be uncoupled from its function outside of cilia; a cilia-excluded ARL13B variant (V358A) that retains all known biochemical activities (GEF for ARL3, etc.) results in normal Shh signal transduction but short cilia lacking ciliary ARL3 and INPP5E, demonstrating that ARL13B's Shh-regulatory function is primarily extraciliary. Knock-in mouse model (V358A cilia-excluded allele), immunofluorescence, Shh pathway readouts, retrograde transport blockade experiments eLife High 32129762
2022 ARL13B interacts with VEGFR2 (by GST-fusion protein-protein interaction and Co-IP), and regulates membrane and ciliary localization of VEGFR2, thereby activating its downstream signaling in endothelial cells. Additionally, ARL13B enhances VEGFA expression by activating Hedgehog signaling in glioma cells; this is transcriptionally regulated by ZEB1. GST-pulldown, Co-immunoprecipitation, immunofluorescence, dual-luciferase reporter assay, endothelial conditional KO/OE mouse models Neuro-oncology Medium 36322624
2023 TULP3's tubby domain interacts with the N-terminal amphipathic helix of ARL13B (a ciliary localization sequence) to mediate ciliary trafficking of ARL13B, independently of palmitoylation. This requires TULP3 binding to IFT-A but not phosphoinositides. TULP3-mediated ARL13B trafficking also controls ciliary enrichment of downstream farnesylated and myristoylated effectors. TULP3-knockout cells, rescue with mutants, domain mapping, immunofluorescence, biochemical interaction assays Molecular biology of the cell High 36652335
2023 Rab8-GDP (but not Rab8-GTP) and TNPO1 simultaneously and directly bind to the C-terminal 17-amino acid ciliary targeting sequence (CTS) of Arl13b containing the RVEP motif; Rab8-GDP enhances the TNPO1-CTS interaction. The RVEP motif is essential for these interactions, and knockdown of Rab8 or TNPO1 decreases ciliary localization of endogenous Arl13b. Pulldown assays with cell lysates and purified recombinant proteins, TurboID-based proximity ligation, truncation/point mutation mapping, RNAi knockdown The Journal of biological chemistry High 36907439
2025 Ciliary ARL13B is essential for body weight regulation in adult mice; cilia-excluded ARL13B (V358A) mice are hyperphagic, obese, and insulin resistant. ARL13B's ARL3 GEF activity is not required for body weight regulation. Induced re-expression of wild-type ARL13B (which localizes to cilia) in 4-week-old obese mice rescues obesity and metabolic impairments, indicating a role in adult homeostatic signaling within cilia. Knock-in mouse models (V358A cilia-excluded, R79Q GEF-deficient), conditional inducible re-expression, metabolic phenotyping (body weight, insulin resistance, hyperphagia) bioRxivpreprint High 37577625
2025 Ciliary ARL13B and its ARL3 GEF activity are required for Pkd1-dependent renal cystogenesis; loss of ciliary ARL13B (V358A) or mutation of the ARL3 GEF-critical residue (R79Q) suppresses Pkd1-dependent cysts, reducing kidney size, cystic index, BUN, renal fibrosis, injury markers, and β-catenin/cyclin D1 levels. Two distinct Arl13b knock-in alleles crossed with Pkd1-deficient adult mouse model, histology, BUN measurements, fibrosis staining, immunofluorescence, Western blotting bioRxivpreprint Medium
2025 Ciliary ARL13B is required for cone photoreceptor function and outer segment morphology; the cilia-excluded V358A variant causes early loss of cone-mediated vision followed by rod vision decline, shortened cone axonemes, structural cone outer segment abnormalities, mislocalization of IFT88 and TULP1 in photoreceptors. The GEF-impaired R79Q variant does not cause similar photoreceptor functional changes. Knock-in mouse models (V358A and R79Q), ERG, immunohistochemistry, transmission electron microscopy The Journal of neuroscience High 40721319
2025 ARL13B males rescued from embryonic lethality by ARL13B-Cerulean fail to sire offspring, revealing a role for ARL13B in spermatogenesis. Conditional knock-in rescue mouse model (Arl13bhnn/hnn expressing ARL13B-Cerulean), breeding assays Journal of cell science Medium 40916698
2025 Complete ARL13B knockout abolishes primary ciliogenesis entirely (not just shortens cilia) in multiple cell lines, and also abolishes cellular response to SMO-mediated Hedgehog stimulation. Multiple regions of ARL13B are necessary for rescue. CRISPR/Cas9 knockout cell lines, immunofluorescence for cilia, Hedgehog stimulation assays, rescue with truncation mutants Scientific reports Medium 40707593
2025 PRPF8 regulates alternative splicing of ARL13B; loss of PRPF8 increases expression of an ARL13B isoform lacking exon 9. Overexpression of the exon-9-lacking ARL13B isoform in zebrafish perturbs cilium formation and causes laterality defects. The shorter ARL13B isoform lacks interactions with intraflagellar transport proteins. Mouse and zebrafish mutant analysis, RNA splicing assays, zebrafish overexpression of alternative isoform, protein interaction studies bioRxivpreprint Medium 40501629
2018 ARL13B localizes to the ciliary membrane and is required in the photoreceptor connecting cilium; loss of ARL13B disrupts proper basal body docking at inner segments and prevents photoreceptor outer segment disc formation (established by conditional KO). Conditional knockout mice, electron microscopy, immunofluorescence The Journal of neuroscience High 30573647
2012 Arl13b is required non-autonomously for BMP signaling and Wnt ligand expression in the dorsal neural tube; dorsal patterning defects in Arl13b(hnn) mutants result from abnormal Shh signaling environment that indirectly disrupts BMP signaling, while downstream Wnt signaling remains normal. Mouse mutant analysis (Arl13b(hnn)), in situ hybridization, immunofluorescence for BMP/Wnt pathway components Developmental biology Medium 21539826
2012 ARL13B (via its effect on Gli activator/repressor balance) controls a critical period of neural tube patterning before E10.5; temporal deletion experiments show that improperly patterned cells recover to wild-type pattern by E12.5, and this recovery requires Gli3 (the primary Gli repressor), establishing ARL13B as an uncoupler of GliA and GliR regulation. Conditional/temporal deletion of Arl13b in mouse, genetic epistasis with Gli3, neural tube patterning assays Development (Cambridge, England) Medium 23014696
2022 PAK2 signaling in zebrafish regulates ARL13B expression and ciliogenesis in brain endothelial cells; overexpression of ARL13B-GFP rescues cilia numbers and cerebral hemorrhage in pak2a (redhead) mutants. In primary human brain microvascular ECs, PDGF-BB and VEGF-A trigger PAK2-ARL13B ciliogenesis signaling through VEGFR-2. Zebrafish genetic model, mRNA overexpression rescue, primary EC culture, biochemical signaling assays Biochemical pharmacology Medium 35700757

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome. American journal of human genetics 318 18674751
2011 Arl13b regulates ciliogenesis and the dynamic localization of Shh signaling proteins. Molecular biology of the cell 244 21976698
2012 ARL13B, PDE6D, and CEP164 form a functional network for INPP5E ciliary targeting. Proceedings of the National Academy of Sciences of the United States of America 199 23150559
2012 Arl13b in primary cilia regulates the migration and placement of interneurons in the developing cerebral cortex. Developmental cell 197 23153492
2010 Joubert syndrome Arl13b functions at ciliary membranes and stabilizes protein transport in Caenorhabditis elegans. The Journal of cell biology 162 20231383
2015 A G-protein activation cascade from Arl13B to Arl3 and implications for ciliary targeting of lipidated proteins. eLife 128 26551564
2009 Cilia localization is essential for in vivo functions of the Joubert syndrome protein Arl13b/Scorpion. Development (Cambridge, England) 124 19906870
2013 Active transport and diffusion barriers restrict Joubert Syndrome-associated ARL13B/ARL-13 to an Inv-like ciliary membrane subdomain. PLoS genetics 88 24339792
2016 Regulation of ciliary retrograde protein trafficking by the Joubert syndrome proteins ARL13B and INPP5E. Journal of cell science 81 27927754
2015 Arl13b and the exocyst interact synergistically in ciliogenesis. Molecular biology of the cell 71 26582389
2020 ARL13B regulates Sonic hedgehog signaling from outside primary cilia. eLife 70 32129762
2018 Axoneme polyglutamylation regulated by Joubert syndrome protein ARL13B controls ciliary targeting of signaling molecules. Nature communications 70 30120249
2014 A function for the Joubert syndrome protein Arl13b in ciliary membrane extension and ciliary length regulation. Developmental biology 70 25448689
2017 Palmitoylation of the ciliary GTPase ARL13b is necessary for its stability and its role in cilia formation. The Journal of biological chemistry 52 28848045
2018 TULP3 is required for localization of membrane-associated proteins ARL13B and INPP5E to primary cilia. Biochemical and biophysical research communications 51 30583862
2014 Identification of a novel ARL13B variant in a Joubert syndrome-affected patient with retinal impairment and obesity. European journal of human genetics : EJHG 51 25138100
2012 Arl13b regulates endocytic recycling traffic. Proceedings of the National Academy of Sciences of the United States of America 51 23223633
2017 Biochemical characterization of purified mammalian ARL13B protein indicates that it is an atypical GTPase and ARL3 guanine nucleotide exchange factor (GEF). The Journal of biological chemistry 48 28487361
2019 The Ciliary Protein Arl13b Functions Outside of the Primary Cilium in Shh-Mediated Axon Guidance. Cell reports 47 31825820
2018 Disruption of the ciliary GTPase Arl13b suppresses Sonic hedgehog overactivation and inhibits medulloblastoma formation. Proceedings of the National Academy of Sciences of the United States of America 44 29378965
2018 ARL13B, a Joubert Syndrome-Associated Protein, Is Critical for Retinogenesis and Elaboration of Mouse Photoreceptor Outer Segments. The Journal of neuroscience : the official journal of the Society for Neuroscience 44 30573647
2023 ARL13B promotes angiogenesis and glioma growth by activating VEGFA-VEGFR2 signaling. Neuro-oncology 40 36322624
2011 Disrupted dorsal neural tube BMP signaling in the cilia mutant Arl13b hnn stems from abnormal Shh signaling. Developmental biology 39 21539826
2014 Visualization of astrocytic primary cilia in the mouse brain by immunofluorescent analysis using the cilia marker Arl13b. Acta medica Okayama 38 25519025
2012 Temporal deletion of Arl13b reveals that a mispatterned neural tube corrects cell fate over time. Development (Cambridge, England) 38 23014696
2014 Arl13b and the non-muscle myosin heavy chain IIA are required for circular dorsal ruffle formation and cell migration. Journal of cell science 37 24777479
2017 Arl13b Promotes Gastric Tumorigenesis by Regulating Smo Trafficking and Activation of the Hedgehog Signaling Pathway. Cancer research 35 28611043
2014 Structural insights into the small G-protein Arl13B and implications for Joubert syndrome. The Biochemical journal 34 24168557
2019 Ciliary genes arl13b, ahi1 and cc2d2a differentially modify expression of visual acuity phenotypes but do not enhance retinal degeneration due to mutation of cep290 in zebrafish. PloS one 33 30970040
2023 Interactions between TULP3 tubby domain and ARL13B amphipathic helix promote lipidated protein transport to cilia. Molecular biology of the cell 32 36652335
2018 The Joubert syndrome protein ARL13B binds tubulin to maintain uniform distribution of proteins along the ciliary membrane. Journal of cell science 30 29592971
2017 Reduced primary cilia length and altered Arl13b expression are associated with deregulated chondrocyte Hedgehog signaling in alkaptonuria. Journal of cellular physiology 26 28158906
2016 Arl13b Interacts With Vangl2 to Regulate Cilia and Photoreceptor Outer Segment Length in Zebrafish. Investigative ophthalmology & visual science 26 27571019
2016 The ciliary GTPase Arl13b regulates cell migration and cell cycle progression. Cell adhesion & migration 17 26963749
2021 Smoothened and ARL13B are critical in mouse for superior cerebellar peduncle targeting. Genetics 16 34132778
2022 Arl13b controls basal cell stemness properties and Hedgehog signaling in the mouse epididymis. Cellular and molecular life sciences : CMLS 14 36261680
2019 Ahi1 promotes Arl13b ciliary recruitment, regulates Arl13b stability and is required for normal cell migration. Journal of cell science 14 31391239
2020 The Joubert Syndrome Gene arl13b is Critical for Early Cerebellar Development in Zebrafish. Neuroscience bulletin 13 32812127
2019 Arl13b Regulates Breast Cancer Cell Migration and Invasion by Controlling Integrin-Mediated Signaling. Cancers 13 31569511
2012 Defective Nodal and Cerl2 expression in the Arl13b(hnn) mutant node underlie its heterotaxia. Developmental biology 12 22554696
2024 Postnatal Dynamic Ciliary ARL13B and ADCY3 Localization in the Mouse Brain. Cells 11 38334651
2022 Ciliogenesis mechanisms mediated by PAK2-ARL13B signaling in brain endothelial cells is responsible for vascular stability. Biochemical pharmacology 11 35700757
2022 TMEM67 is required for the gating function of the transition zone that controls entry of membrane-associated proteins ARL13B and INPP5E into primary cilia. Biochemical and biophysical research communications 11 36334440
2017 A novel Cre-inducible knock-in ARL13B-tRFP fusion cilium reporter. Genesis (New York, N.Y. : 2000) 10 28948682
2017 A novel homozygous ARL13B variant in patients with Joubert syndrome impairs its guanine nucleotide-exchange factor activity. European journal of human genetics : EJHG 10 29255182
2023 Rab8 and TNPO1 are ciliary transport adaptors for GTPase Arl13b by interacting with its RVEP motif containing ciliary targeting sequence. The Journal of biological chemistry 9 36907439
2023 Increasing Ciliary ARL13B Expression Drives Active and Inhibitor-Resistant Smoothened and GLI into Glioma Primary Cilia. Cells 7 37830570
2018 Developmental expression of the zebrafish Arf-like small GTPase paralogs arl13a and arl13b. Gene expression patterns : GEP 7 30009987
2018 The unusual flagellar-targeting mechanism and functions of the trypanosome ortholog of the ciliary GTPase Arl13b. Journal of cell science 6 30097558
2025 Ciliary ARL13B is essential for body weight regulation in adult mice. bioRxiv : the preprint server for biology 5 37577625
2024 Novel compound heterozygous variants in ARL13B lead to Joubert syndrome. Journal of cellular physiology 5 38219074
2019 The Dynamic and Complex Role of the Joubert Syndrome-Associated Ciliary Protein, ADP-Ribosylation Factor-Like GTPase 13B (ARL13B) in Photoreceptor Development and Maintenance. Advances in experimental medicine and biology 5 31884661
2025 Knocking out ARL13B completely abolishes primary ciliogenesis in cell lines. Scientific reports 3 40707593
2024 ARL13B promotes cell cycle through the sonic hedgehog signaling pathway to alleviate nerve damage during cerebral ischemia/reperfusion in rats. Biochemical pharmacology 3 39038552
2025 ARL13B regulates juxtaposed cilia-cilia elongation in BBSome dependent manner in Caenorhabditis elegans. iScience 2 39925426
2025 ARL13B-Cerulean rescues Arl13b-null mouse from embryonic lethality and reveals a role for ARL13B in spermatogenesis. Journal of cell science 2 40916698
2023 Arl13b promotes the proliferation, migration, osteogenesis, and mechanosensation of osteoblasts. Tissue & cell 2 37058812
2025 ARL13B-Cerulean rescues Arl13b-null mouse from embryonic lethality and reveals a role for ARL13B in spermatogenesis. bioRxiv : the preprint server for biology 1 40196635
2025 Volumetric Imaging and Analysis of Primary Cilia in Musculoskeletal Tissue using the ARL13B-CENTRIN-2 Mouse Model. Journal of visualized experiments : JoVE 0 40228007
2025 The RNA splicing factor PRPF8 is required for left-right organiser cilia differentiation and determination of cardiac left-right asymmetry via regulation of Arl13b splicing. bioRxiv : the preprint server for biology 0 40501629
2025 Ciliary ARL13B Is Essential for Vision and Morphogenesis of Cone Outer Segments. The Journal of neuroscience : the official journal of the Society for Neuroscience 0 40721319
2025 The Role of ARL13B in Mitochondrial Homeostasis in Cultured Human Corneal Endothelial Cells. Investigative ophthalmology & visual science 0 41091001
2025 Unraveling the Genetic Links Between Polycystic Kidney Disease and Hypertension Through ARL13B. International journal of nephrology and renovascular disease 0 41158202
2025 Loss of a primary cilia protein ARL13B promotes TGFβ-1 induced EMT of RPE in proliferative vitreoretinopathy via increasing Smad3 expression. Frontiers in cell and developmental biology 0 41425088
2024 Induction of IMPDH-Based Cytoophidia by a Probable IMP-Dependent ARL13B-IMPDH Interaction. Biochemistry. Biokhimiia 0 39865040

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