Affinage

GPRC5B

G-protein coupled receptor family C group 5 member B · UniProt Q9NZH0

Length
403 aa
Mass
44.8 kDa
Annotated
2026-06-10
38 papers in source corpus 23 papers cited in narrative 22 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

GPRC5B is a constitutively active, lipid raft-associated orphan family C GPCR with only a short extracellular domain that broadly couples membrane lipid and inflammatory state to intracellular signaling across metabolic, vascular, and neural tissues (PMID:10945465, PMID:10783259, PMID:23169819). Its core signaling output depends on tyrosine phosphorylation of its cytoplasmic C-terminus by the Src-family kinase Fyn, which then binds the phosphorylated tail through its SH2 domain to drive a self-sustaining NF-κB–IKKε inflammatory feedback loop and ERK1/2 activation; a mutant lacking the Fyn-SH2 binding site cannot initiate this loop, and GPRC5B-deficient mice are protected from diet-induced obesity and insulin resistance (PMID:23169819, PMID:35033869). This phosphorylation node is negatively gated by caveolin-1, which binds the GPRC5B cytoplasmic tail and suppresses its tyrosine phosphorylation and downstream NF-κB signaling (PMID:30086884). Fyn activity downstream of GPRC5B also phosphorylates sphingomyelin synthase 2 (SMS2), stabilizing it against ubiquitination and driving DAG-dependent JNK activation that impairs insulin action under lipid stress (PMID:30343189). Beyond its own signaling, GPRC5B physically associates with and modulates partner GPCRs: it sequesters the prostacyclin receptor IP in vascular smooth muscle to restrain cAMP-driven relaxation and dedifferentiation (PMID:31941358), and dimerizes with the prostaglandin E receptor EP2 in macrophages to enhance EP2-mediated cAMP anti-inflammatory signaling (PMID:39920161). GPRC5B has additional cell-type-specific roles, including maintenance of mature β-cell identity through cAMP/CREB-dependent MafA expression (PMID:40906536) and a constitutive activity that is inhibited by MLC1 and coupled to GlialCAM/β-arrestin 2 in astrocyte volume regulation (PMID:34100078, PMID:41314544); heterozygous de novo GPRC5B variants disrupting astrocyte cell-volume regulation cause a megalencephalic leukoencephalopathy (MLC)-related disorder (PMID:37143309). Its developmental and tissue-homeostatic functions, including cortical neuronal fate determination via β-catenin (PMID:24089469) and cartilage homeostasis via AKT–mTOR–autophagy (PMID:37521864), extend the receptor's reach but are less mechanistically resolved.

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2000 Medium

    Established GPRC5B as a structurally distinct orphan family C GPCR, defining its molecular identity and cell-surface disposition before any function was known.

    Evidence Homology searching and transient transfection of epitope-tagged constructs in HEK293T cells

    PMID:10783259 PMID:10945465

    Open questions at the time
    • No ligand identified
    • No signaling activity demonstrated
    • Function entirely unknown at this stage
  2. 2002 Medium

    Confirmed endogenous protein expression and CNS-enriched distribution, anchoring later neural phenotypes to a real expression pattern.

    Evidence Western blot, immunocytochemistry, and immunohistochemistry in rat brain

    PMID:12393273

    Open questions at the time
    • No functional assay
    • Brain-region expression does not establish cell-type-specific roles
  3. 2012 High

    Defined the central signaling mechanism: Fyn phosphorylates the GPRC5B C-terminal tyrosines and is recruited via its SH2 domain to sustain an NF-κB–IKKε inflammatory loop, linking the receptor to obesity-associated insulin resistance.

    Evidence Knockout mice in diet-induced obesity, Fyn SH2-domain interaction mapping, Fyn-binding-site mutant, NF-κB/IKKε assays, lipid raft fractionation

    PMID:23169819

    Open questions at the time
    • Upstream activating signal/ligand undefined
    • Mechanism connecting raft localization to Fyn phosphorylation not detailed
  4. 2013 Medium

    Extended GPRC5B function into development and pancreatic physiology, showing it directs cortical progenitor neuronal fate via β-catenin and negatively modulates islet insulin secretion.

    Evidence GPRC5B depletion in mouse neocortex with fate analysis; lentiviral shRNA knockdown in murine islets and MIN6 cells with secretion and apoptosis assays

    PMID:24089469 PMID:24404583

    Open questions at the time
    • Molecular link between GPRC5B and β-catenin not resolved
    • Mechanism of insulin-secretion modulation not defined
  5. 2014 Medium

    Demonstrated intercellular transfer of GPRC5B via exosomes that promotes ERK-dependent tubulogenesis, revealing a non-cell-autonomous mode of action.

    Evidence 3D MDCK cyst model, exosome isolation and uptake, ERK1/2 phosphorylation and tubulogenesis assays

    PMID:24412205

    Open questions at the time
    • How exosomal GPRC5B activates ERK in recipient cells unknown
    • Single epithelial model
  6. 2018 High

    Resolved how GPRC5B-Fyn signaling reaches lipid metabolism and identified caveolin-1 as a negative regulator, building a two-sided control of the phosphorylation node.

    Evidence Co-IP of GPRC5B–SMS2, SMS2-KO MEFs with phosphomimetic reconstitution, ubiquitination and JNK/insulin readouts; Cav1 co-IP, domain mapping, Cav1-deficient cells under palmitate stress

    PMID:30086884 PMID:30343189

    Open questions at the time
    • How metabolic stress augments GPRC5B–SMS2 interaction unknown
    • Stoichiometry of Cav1 regulation not quantified
  7. 2018 Medium

    Showed a cerebellar developmental role, with GPRC5B required for Purkinje cell axonal/synaptic integrity, mitochondrial ROS control, synaptic plasticity, and motor learning.

    Evidence Gprc5b-/- mice, primary PC culture, ROS measurement and pharmacological reduction, patch-clamp LTP/LTD, rotarod and HOKR tests

    PMID:29481883

    Open questions at the time
    • Molecular link between GPRC5B and mitochondrial ROS unknown
    • Whether this uses the Fyn/NF-κB axis untested
  8. 2019 Medium

    Generalized the NF-κB inflammatory role beyond adipose to kidney podocytes, with cell-type-specific knockout protecting against inflammatory nephropathy.

    Evidence Podocyte-specific Gprc5b KO mice, LPS nephropathy model, proteinuria, inflammatory cell quantification, RNA-seq, in vitro NF-κB assays

    PMID:31285284

    Open questions at the time
    • Whether the same Fyn-SH2 mechanism operates in podocytes not directly tested
  9. 2020 High

    Established GPRC5B as a direct modulator of partner GPCR signaling, sequestering the prostacyclin receptor IP to restrain cAMP-driven vasorelaxation and SMC dedifferentiation in hypertension and atherosclerosis.

    Evidence SMC-specific inducible Gprc5b-KO mice, GPRC5B–IP co-IP, IP membrane fractionation, cAMP assays, ex vivo contractility, hypertension and atherosclerosis models with IP antagonist rescue

    PMID:31941358

    Open questions at the time
    • Structural basis of GPRC5B–IP interaction not defined here
    • Relationship to Fyn signaling in this context unclear
  10. 2021 Medium

    Connected GPRC5B to the astrocyte volume-regulation machinery through direct GlialCAM and MLC1 interactions controlling ClC-2/VRAC channel activity, framing its relevance to leukoencephalopathy.

    Evidence GlialCAM interactome MS with co-IP validation, siRNA in primary astrocytes, ClC-2 and VRAC electrophysiology, osmolarity/K+ modulation

    PMID:34100078

    Open questions at the time
    • Whether GPRC5B regulates channels directly or via MLC1/GlialCAM abundance unclear
    • No structural interaction map
  11. 2022 Medium

    Confirmed in vascular endothelium and VSMCs that GPRC5B drives ERK1/2 and NF-κB activation via Fyn, promoting pro-inflammatory cytokine and adhesion-molecule expression under hyperglycemic/cytokine stress.

    Evidence Overexpression and siRNA knockdown in endothelial cells and VSMCs, ERK/NF-κB assays, Fyn co-IP, cytokine and MMP-9 measurements

    PMID:35033869

    Open questions at the time
    • Causal ordering of ERK vs NF-κB activation not resolved
    • Single lab
  12. 2023 Medium

    Provided human genetic and functional evidence linking GPRC5B to a megalencephalic leukoencephalopathy-spectrum disorder via disrupted astrocyte cell-volume regulation.

    Evidence Genetic identification of de novo GPRC5B variants in MLC patients, human brain IHC, cell-volume measurements in patient-derived lymphoblasts, electrophysiology

    PMID:37143309

    Open questions at the time
    • Whether variants are gain- or loss-of-function not fully resolved at this stage
    • Genotype–phenotype correlation limited
  13. 2023 Medium

    Identified a protective role in cartilage homeostasis acting through AKT–mTOR–autophagy signaling, expanding GPRC5B's tissue-homeostatic functions.

    Evidence Gprc5b-KO mice in DMM osteoarthritis model, lentiviral overexpression, chondrocyte gene expression, AKT/mTOR/autophagy assays

    PMID:37521864

    Open questions at the time
    • How GPRC5B engages AKT-mTOR not mechanistically defined
    • Receptor activation trigger in chondrocytes unknown
  14. 2025 High

    Resolved a second partner-GPCR mechanism in macrophages, with GPRC5B-EP2 dimerization (mapped by modelling and mutagenesis) enhancing anti-inflammatory cAMP signaling and restraining macrophage activity.

    Evidence Myeloid-specific GPRC5B-KO mice, co-IP, in silico docking, dimerization-residue mutagenesis, decoy peptides, cAMP/migration/phagocytosis assays, peritonitis model

    PMID:39920161

    Open questions at the time
    • Whether GPRC5B modulates EP2 oppositely to IP across tissues not reconciled
    • No experimental structure of the dimer
  15. 2025 Medium

    Defined GPRC5B's constitutive activity and its regulation by MLC1 (via oligomerization) and GlialCAM/β-arrestin 2, and characterized how MLC-associated mutants alter membrane stability and GlialCAM localization.

    Evidence Constitutive activity and β-arrestin 2 recruitment assays, oligomerization/domain analysis, MLC-mutant localization, biochemical fractionation

    PMID:41314544

    Open questions at the time
    • Endogenous ligand or stimulus controlling constitutive activity unknown
    • Downstream effectors of β-arrestin recruitment not mapped
  16. 2025 Medium

    Showed GPRC5B sustains mature β-cell identity in obesity via cAMP/CREB-dependent MafA expression, with temporal ordering placing CREB phosphorylation upstream of MafA loss.

    Evidence Tamoxifen-inducible β-cell-specific GPRC5B-KO mice on high-fat diet, scRNA-seq, CREB phosphorylation, MafA Western/RT-PCR, glucose tolerance and insulin secretion

    PMID:40906536

    Open questions at the time
    • How GPRC5B couples to cAMP/CREB in β-cells not defined
    • Apparent contrast with earlier islet knockdown phenotype unreconciled
  17. 2025 Medium

    Implicated GPRC5B as a brake on endothelial p38 MAPK signaling by restraining MKK3/6 and maintaining DUSP1, with loss accelerating angiogenesis and tumor growth.

    Evidence Endothelial loss-of-function in vitro and in vivo, MKK3/6 and DUSP1 assays, p38 inhibitor rescue, tube formation, migration, tumor xenograft

    PMID:41734845

    Open questions at the time
    • Mechanism by which GPRC5B regulates DUSP1 and MKK3/6 unknown
    • Relationship to the pro-inflammatory ERK/NF-κB role unresolved
  18. 2025 Medium

    Linked RA signaling to GPRC5B in suppression of adult hippocampal neurogenesis and depressive-like behavior, with KO mice resistant to RA effects.

    Evidence Gprc5b-KO mice, RA treatment, behavioral assays, BrdU/EdU neurogenesis quantification, SGZ expression analysis

    PMID:41204039

    Open questions at the time
    • Downstream signaling mediating neurogenesis suppression undefined
    • Whether RA directly regulates GPRC5B transcription unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The endogenous ligand or activating stimulus of GPRC5B and the structural basis for how its constitutive activity, partner-GPCR dimerization, and Fyn-dependent versus cAMP-dependent outputs are selected across tissues remain unresolved.
  • No endogenous ligand identified
  • No experimental structure of GPRC5B or its GPCR heterodimers
  • Context-dependent output selection (NF-κB/ERK vs cAMP/CREB vs p38) not mechanistically explained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0060089 molecular transducer activity 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1430728 Metabolism 2
Partners
CAV1FYNGLIALCAMMLC1PTGER2PTGIRSMS2

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 GPRC5B (RAIG-2) is a seven-transmembrane orphan receptor classified within the type 3/family C GPCR subfamily; it has only a short N-terminal extracellular domain (in contrast to other family C GPCRs), contains a signal peptide, and localizes to the cell surface when transiently transfected in HEK293T cells. Homology searching, sequence analysis, transient transfection with epitope-tagged constructs in HEK293T cells Genomics Medium 10783259 10945465
2002 GPRC5B protein migrates at ~68 kDa on Western blot (close to predicted MW) and immunocytochemical analysis of GPRC5B-transfected cells confirmed cell-surface localization; immunohistochemical analysis in rat brain showed highest expression in neocortex, hippocampus, cerebellar granule cell layer, and spinal cord. Western blot with affinity-purified antisera, immunocytochemistry, immunohistochemistry Brain research. Molecular brain research Medium 12393273
2012 GPRC5B is a lipid raft-associated transmembrane protein. It is phosphorylated on multiple tyrosine residues in its carboxyl terminus by the Src-family kinase Fyn, and this phosphorylation enables direct recruitment of Fyn through its SH2 domain. This GPRC5B–Fyn interaction is required to initiate and sustain a positive NF-κB–IKKε inflammatory signaling feedback loop in adipose tissue; a GPRC5B mutant lacking the Fyn-SH2 binding site fails to activate this loop. GPRC5B-deficient mice are protected from diet-induced obesity and insulin resistance. GPRC5B knockout mice (diet-induced obesity model), phosphorylation analysis, direct interaction assay (Fyn SH2 domain binding), site-directed mutant lacking Fyn-binding site, NF-κB/IKKε signaling assays, lipid raft fractionation Science signaling High 23169819
2013 GPRC5B is present at the ventricular surface of cortical progenitors in the developing mouse neocortex; its depletion causes cortical progenitors to fail neuronal fate adoption and instead become astrocytes; GPRC5B-mediated signaling is required for proper β-catenin pathway regulation in progenitor fate decisions. GPRC5B depletion in developing mouse neocortex, neuronal fate analysis, β-catenin signaling assays Development (Cambridge, England) Medium 24089469
2013 GPRC5B acts as a negative modulator of insulin secretion in pancreatic islets; lentiviral shRNA-mediated knockdown of Gprc5b in mouse islets strongly increased basal and glucose-stimulated insulin secretion and enhanced glutamate-potentiated secretion; knockdown also protected MIN6 β-cells against cytokine-induced apoptosis. Lentiviral shRNA knockdown of Gprc5b in intact murine islets, insulin secretion assays, MIN6 cytokine-induced apoptosis assay Biochemical and biophysical research communications Medium 24404583
2014 GPRC5B is packaged into exosomes by HGF-treated MDCK epithelial cysts and released into the cyst lumen; exosomal GPRC5B is taken up by nearby cells and, together with HGF, promotes ERK1/2 activation and tubulogenesis in 3D extracellular matrix gels under conditions where tubulogenesis would otherwise not occur. 3D MDCK cyst model, exosome isolation and uptake assays, ERK1/2 phosphorylation assays, tubulogenesis assays Current biology : CB Medium 24412205
2018 GPRC5B mediates phosphorylation of sphingomyelin synthase 2 (SMS2) by Fyn. Lipid-induced metabolic stress augments GPRC5B–SMS2 interaction, leading to SMS2 phosphorylation that reduces its ubiquitination and increases its protein abundance. SMS2-generated DAG in sphingomyelin synthesis activates JNK, which impairs insulin signaling; phosphomimetic SMS2 is sufficient to impair insulin action in SMS2-KO MEFs under metabolic stress. Co-immunoprecipitation of GPRC5B–SMS2 complex, SMS2-KO MEFs, phosphomimetic SMS2 reconstitution, ubiquitination assays, JNK and insulin signaling readouts iScience High 30343189
2018 GPRC5B promotes Purkinje cell (PC) axonal development and synapse formation with deep cerebellar nuclear (DCN) neurons; in Gprc5b-/- mice, PCs develop distal axonal swellings containing misshapen mitochondria with excessive reactive oxygen species (ROS); pharmacological reduction of ROS prevents these swellings in Gprc5b-/- PC cultures. LTP at mossy fiber–DCN synapses is attenuated and long-term motor learning is impaired in Gprc5b-/- mice. Gprc5b-/- mice, primary PC culture, ROS measurement, pharmacological ROS reduction, patch-clamp electrophysiology (LTD/LTP), rotarod and HOKR motor learning tests Neuroscience research Medium 29481883
2018 Caveolin-1 (Cav1) directly interacts with the cytoplasmic tail of GPRC5B via Cav1's C-terminal domain (GPRC5B lacks a conventional caveolin-binding motif), and this interaction suppresses GPRC5B tyrosine phosphorylation, thereby reducing GPRC5B-mediated NF-κB signaling; cells lacking Cav1 show highly elevated GPRC5B phosphorylation, and exogenous Cav1 expression inhibits it. Co-immunoprecipitation, domain mapping, Cav1-deficient cell lines, exogenous Cav1 expression, NF-κB signaling assays under palmitate stress Biochemical and biophysical research communications Medium 30086884
2019 GPRC5B regulates inflammatory response in podocytes via NF-κB signaling; podocyte-specific Gprc5b knockout mice are partially protected from LPS-induced proteinuria and inflammatory cell recruitment. RNA-seq of knockout mice and in vitro podocyte experiments confirmed GPRC5B modulates NF-κB-dependent gene expression. Podocyte-specific Gprc5b KO mice, LPS-induced nephropathy model, proteinuria measurement, inflammatory cell quantification, RNA-seq, in vitro podocyte NF-κB assays Journal of the American Society of Nephrology : JASN Medium 31285284
2020 GPRC5B physically interacts with the prostacyclin receptor (IP) in vascular smooth muscle cells (SMCs), and GPRC5B knockdown increases membrane localization of IP, leading to enhanced IP-dependent cAMP production and SMC relaxation. SMC-specific Gprc5b-KO mice are protected from arterial hypertension, and this protection is abrogated by IP antagonists. GPRC5B deficiency also prevents SMC dedifferentiation during atherosclerosis, reducing plaque load. SMC-specific tamoxifen-inducible Gprc5b-KO mice, co-immunoprecipitation (GPRC5B–IP interaction), membrane fractionation of IP, cAMP assays, mesenteric artery ex vivo contractility, arterial hypertension model, atherosclerosis model Circulation High 31941358
2021 GPRC5B directly interacts with GlialCAM (validated by co-immunoprecipitation from brain interactome); reduction of GPRC5B in primary astrocytes downregulates MLC1 and GlialCAM proteins and impairs activation of the chloride channels ClC-2 and VRAC. The interaction between GPRC5B and MLC1 is dynamically regulated by changes in osmolarity and potassium concentration. GlialCAM interactome proteomics (MS), co-immunoprecipitation validation, siRNA knockdown in primary astrocytes, ClC-2 and VRAC electrophysiology, osmolarity/K+ modulation assays Human molecular genetics Medium 34100078
2022 GPRC5B overexpression in endothelial cells and VSMCs increases phosphorylation of ERK1/2 and activates NF-κB through a direct interaction with the tyrosine kinase Fyn; GPRC5B knockdown attenuates expression of pro-inflammatory cytokines (TNFα, IL-1β, IL-6) and adhesion molecules (ICAM-1, VCAM-1) and reduces MMP-9 expression/activity in response to high glucose and cytokines. Adenoviral/plasmid GPRC5B overexpression and siRNA knockdown in endothelial cells and VSMCs, ERK1/2 and NF-κB phosphorylation assays, co-immunoprecipitation with Fyn, cytokine and MMP-9 measurements Biochemical and biophysical research communications Medium 35033869
2023 GPRC5B is expressed in astrocyte endfeet in human brain; heterozygous de novo GPRC5B variants cause disrupted cell volume regulation (demonstrated in patient-derived lymphoblasts); GPRC5B functionally interacts with ion channels involved in astrocyte volume regulation. Genetic identification of GPRC5B variants in MLC patients, immunohistochemistry of human brain, cell volume measurements in patient-derived lymphoblasts, electrophysiology Brain : a journal of neurology Medium 37143309
2025 GPRC5B physically interacts with GPCRs of the prostanoid receptor family, particularly prostaglandin E receptor 2 (EP2), in macrophages, resulting in enhanced EP2-mediated cAMP signaling and anti-inflammatory effects; in GPRC5B-deficient macrophages, EP2 anti-inflammatory signaling is diminished, causing macrophage hyperactivity (increased migration and phagocytosis). In silico modelling identified residues mediating GPRC5B/EP2 dimerization, and their mutation abolishes facilitation of EP2 signaling; decoy peptides mimicking the interacting sequence reduce GPRC5B-mediated EP2-induced cAMP signaling. Myeloid-specific GPRC5B-KO mice, co-immunoprecipitation, in silico docking/modelling, site-directed mutagenesis of dimerization residues, cAMP assays, migration and phagocytosis assays, peritonitis model Nature communications High 39920161
2025 GPRC5B exhibits constitutive activity that is inhibited by MLC1, likely through interference with GPRC5B oligomerization. GlialCAM enhances β-arrestin 2 recruitment to GPRC5B, leading to GlialCAM mislocalization from cell-cell junctions. MLC-associated GPRC5B mutants show enhanced plasma membrane stability and increased affinity for GlialCAM but retain normal constitutive activity and responsiveness to MLC1; coexpression with these mutants does not induce GlialCAM mislocalization. Constitutive activity assays, β-arrestin 2 recruitment assays, domain/oligomerization analysis, localization studies of MLC-associated mutants, biochemical fractionation The Journal of biological chemistry Medium 41314544
2025 GPRC5B maintains mature β-cell function in obesity through cAMP/CREB-dependent regulation of MafA expression; β-cell-specific GPRC5B-KO mice on high-fat diet show reduced CREB phosphorylation (preceding MafA downregulation), decreased MafA mRNA and protein, reduced MafA target gene expression, loss of mature β-cell phenotype, and impaired insulin secretion and glucose tolerance. Tamoxifen-inducible β-cell-specific GPRC5B-KO mice, high-fat diet, flow cytometry, single-cell RNA-seq, CREB phosphorylation assays, Western blot and RT-PCR for MafA and targets, glucose tolerance tests, insulin secretion assays JCI insight Medium 40906536
2021 GPRC5B expression in cardiac and lung myofibroblasts promotes collagen gene expression; Gprc5b knockdown reduces collagen gene expression in these cells, and Gprc5b expression is associated with and may depend on the actin-MRTF-SRF signaling pathway. siRNA knockdown of Gprc5b in cardiac and lung myofibroblasts, real-time RT-PCR for collagen genes, fibrosis mouse models (in vivo expression), actin-MRTF-SRF pathway analysis Biochemical and biophysical research communications Low 34023784
2025 GPRC5B loss in endothelial cells hyperactivates p38 MAPK signaling by increasing phosphorylation of upstream MKK3/6 kinases while concurrently suppressing the negative-feedback phosphatase DUSP1, resulting in enhanced endothelial proliferation, migration, and tube formation in vitro and accelerated tumor growth and neovascularization in vivo; these phenotypes are rescued by p38 inhibitor SB202190. Endothelial GPRC5B loss-of-function in vitro and in vivo, MKK3/6 and DUSP1 phosphorylation/expression assays, p38 inhibitor rescue, tube formation and migration assays, tumor xenograft model International journal of biological macromolecules Medium 41734845
2026 NSUN2-mediated m5C RNA methylation upregulates GPRC5B mRNA expression in osteosarcoma; GPRC5B in turn suppresses apoptosis and promotes cell proliferation and migration. Knockdown of GPRC5B partially rescues the anti-apoptotic effects of NSUN2, establishing an NSUN2→m5C-GPRC5B anti-apoptotic regulatory axis. meRIP-seq and RNA-seq in osteosarcoma tissues, GPRC5B knockdown and NSUN2 knockdown functional experiments, apoptosis, proliferation, and migration assays Cancer science Low 41846428
2023 GPRC5B promotes cartilage homeostasis; Gprc5b-deficient chondrocytes upregulate catabolic genes and downregulate anabolic genes; Gprc5b-KO mice show more severe OA after destabilization of medial meniscus. Overexpression via lentiviral vectors alleviates cartilage degeneration. Mechanistically, GPRC5B acts through the AKT–mTOR–autophagy signaling pathway. Gprc5b-KO mice (DMM OA model), lentiviral GPRC5B overexpression, in vitro chondrocyte gene expression, AKT/mTOR/autophagy pathway assays Acta pharmaceutica Sinica. B Medium 37521864
2025 GPRC5B mediates retinoic acid (RA)-induced suppression of adult hippocampal neurogenesis and depressive-like behaviors; Gprc5b-KO mice are resilient to RA-induced behavioral effects and show a larger pool of proliferative neuronal stem cells, with RA failing to inhibit neurogenesis in the absence of GPRC5B. RA increases GPRC5B expression specifically in the hippocampal neurogenic subgranular zone. Gprc5b-KO mice, RA treatment, behavioral assays, BrdU/EdU-based neurogenesis quantification, hippocampal SGZ expression analysis Molecular neurobiology Medium 41204039

Source papers

Stage 0 corpus · 38 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Molecular cloning and characterization of two novel retinoic acid-inducible orphan G-protein-coupled receptors (GPRC5B and GPRC5C). Genomics 109 10945465
2000 Sequence and expression pattern of a novel human orphan G-protein-coupled receptor, GPRC5B, a family C receptor with a short amino-terminal domain. Genomics 66 10783259
2012 GPRC5B activates obesity-associated inflammatory signaling in adipocytes. Science signaling 55 23169819
2018 GPRC5B-Mediated Sphingomyelin Synthase 2 Phosphorylation Plays a Critical Role in Insulin Resistance. iScience 42 30343189
2014 Intercellular transfer of GPRC5B via exosomes drives HGF-mediated outward growth. Current biology : CB 39 24412205
2013 The G protein-coupled receptor GPRC5B contributes to neurogenesis in the developing mouse neocortex. Development (Cambridge, England) 36 24089469
2013 GPRC5B a putative glutamate-receptor candidate is negative modulator of insulin secretion. Biochemical and biophysical research communications 30 24404583
2011 Comparative characterization of GPRC5B and GPRC5CLacZ knockin mice; behavioral abnormalities in GPRC5B-deficient mice. Biochemical and biophysical research communications 30 21840300
2023 Aquaporin-4 and GPRC5B: old and new players in controlling brain oedema. Brain : a journal of neurology 25 37143309
2020 Orphan G Protein-Coupled Receptor GPRC5B Controls Smooth Muscle Contractility and Differentiation by Inhibiting Prostacyclin Receptor Signaling. Circulation 25 31941358
2002 Localisation of the GPRC5B receptor in the rat brain and spinal cord. Brain research. Molecular brain research 24 12393273
2021 Identification of the GlialCAM interactome: the G protein-coupled receptors GPRC5B and GPR37L1 modulate megalencephalic leukoencephalopathy proteins. Human molecular genetics 23 34100078
2019 GPRC5b Modulates Inflammatory Response in Glomerular Diseases via NF-κB Pathway. Journal of the American Society of Nephrology : JASN 22 31285284
2020 Roles of GPRC5 family proteins: focusing on GPRC5B and lipid-mediated signalling. Journal of biochemistry 21 32154895
2018 Loss of GPRC5B impairs synapse formation of Purkinje cells with cerebellar nuclear neurons and disrupts cerebellar synaptic plasticity and motor learning. Neuroscience research 19 29481883
2023 GPRC5B protects osteoarthritis by regulation of autophagy signaling. Acta pharmaceutica Sinica. B 15 37521864
2022 The orphan receptor GPRC5B activates pro-inflammatory signaling in the vascular wall via Fyn and NFκB. Biochemical and biophysical research communications 14 35033869
2010 A flanking gene problem leads to the discovery of a Gprc5b splice variant predominantly expressed in C57Bl/6J mouse brain and in maturing neurons. PloS one 13 20436672
2019 The orphan receptor GPRC5B modulates inflammatory and fibrotic pathways in cardiac fibroblasts and mice hearts. Biochemical and biophysical research communications 12 31104767
2018 Identifying Signalling Pathways Regulated by GPRC5B in β-Cells by CRISPR-Cas9-Mediated Genome Editing. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 12 29408822
2018 Caveolin-1 prevents palmitate-induced NF-κB signaling by inhibiting GPRC5B-phosphorylation. Biochemical and biophysical research communications 11 30086884
2014 G protein-coupled receptor, family C, group 5 (GPRC5B) downregulation in spinal cord neurons is involved in neuropathic pain. Korean journal of anesthesiology 11 24729846
2025 Orphan G protein-coupled receptor GPRC5B controls macrophage function by facilitating prostaglandin E receptor 2 signaling. Nature communications 9 39920161
2022 Orphan G-Protein Coupled Receptor GPRC5B Is Critical for Lymphatic Development. International journal of molecular sciences 9 35628521
2022 Comprehensive Spatial Profile of the Orphan G Protein Coupled Receptor GPRC5B Expression in Mouse Brain. Frontiers in neuroscience 8 35812210
2007 Changes in expression and localization of GPRC5B and RARalpha in the placenta and yolk sac during middle to late gestation in mice. The Journal of reproduction and development 7 17652913
2022 Knockdown of GPRC5B alleviates the high glucose-induced inflammation and extracellular matrix deposition of podocyte through inhibiting NF-κB pathway. Allergologia et immunopathologia 6 35257557
2023 GPRC5B (G protein-coupled receptor class C group 5 member B) suppresses glucose starvation-induced apoptosis in head-and-neck squamous cell carcinoma. Biomedical research (Tokyo, Japan) 4 36682796
2021 GPRC5B promotes collagen production in myofibroblasts. Biochemical and biophysical research communications 3 34023784
2025 A Reflux Linked GATA Factor Fulcrum Dictates Lineage Commitment Through GPRC5B During the Esophageal Dysplastic Transition. Cellular and molecular gastroenterology and hepatology 1 40490196
2025 GPRC5B preserves a mature β cell state in obesity by controlling MafA expression. JCI insight 1 40906536
2025 USP44, ZNF454, and GPRC5B ctDNA Methylation Markers in Breast Cancer: Limited Clinical Relevance for Disease Monitoring and Tumor Characteristics. Asia-Pacific journal of clinical oncology 1 40922130
2026 Study on the Role of Long Non-Coding RNA GAS5 in Promoting the Malignant Progression of Prostate Cancer by Regulating miR-12/GPRC5B Signaling Axis. Bulletin of experimental biology and medicine 0 41505048
2026 From clinical evidence to biological mechanisms: GPRC5B as a key mediator of metabolic syndrome-associated prostate cancer. International journal of biological macromolecules 0 41734845
2026 GPRC5B Identified by m5C meRIP-Seq Suppresses Apoptosis in Osteosarcoma Through NSUN2-Mediated RNA Methylation. Cancer science 0 41846428
2025 The orphan receptor GPRC5B promotes macrophage infiltration and an inflammatory plaque phenotype in atherosclerosis. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology 0 41043569
2025 Orphan Receptor GPRC5B Controls Adult Hippocampal Neurogenesis and Affects Retinoic Acid-Mediated Behaviors. Molecular neurobiology 0 41204039
2025 Regulation of the orphan G-protein-coupled receptor GPRC5B by MLC1 and the cell adhesion molecule GlialCAM in megalencephalic leukoencephalopathy. The Journal of biological chemistry 0 41314544

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