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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GPR55
G protein-coupled receptor 55
Chromosome 2 · 2q37.1
NCBI Gene: 9290Ensembl: ENSG00000135898.11HGNC: HGNC:4511UniProt: A8K858
135PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Receptor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membranecannabinoid receptor activityprotein bindingG protein-coupled receptor signaling pathwaysprainpreeclampsiapsoriatic arthritispsoriasis
✦AI Summary

GPR55 is an orphan G protein-coupled receptor that functions as a lipid sensor activated by endogenous lysophosphatidylinositol (LPI) and related lipids 1. Upon activation, GPR55 initiates rapid intracellular signaling through heterotrimeric G13 proteins and ERK pathways, triggering calcium release from intracellular stores and cytoskeletal reorganization via RHOA-mediated stress fiber formation 1. The receptor exhibits broad tissue distribution with roles in metabolic regulation, vascular function, and bone homeostasis 2. Pharmacologically, GPR55 is modulated by diverse ligands including endocannabinoids, phytocannabinoids like cannabidiol, and synthetic agonists 34. In macrophages, GPR55 activation suppresses ABCA1-mediated cholesterol efflux, promoting foam cell formation and atherosclerotic pathology. Clinically, GPR55 dysregulation is implicated in multiple disease states: the LPI/GPR55 axis promotes oncogenic processes including proliferation, migration, and metastasis across cancer types 2, while receptor modulation shows therapeutic promise for epilepsy, pain, inflammation, and metabolic disorders including type 2 diabetes 56. GPR55 and its ligands are emerging as potential biomarkers for cancer diagnosis and progression.

Sources cited
1
GPR55 structure, activation by LPI and ML184, G13 coupling, and orthosteric binding site opening
PMID: 40000629
2
GPR55 role in cancer, LPI/GPR55 axis in proliferation and metastasis, tissue distribution, G12/13 and Gq signaling
PMID: 35500681
3
CBD modulation of GPR55 and therapeutic effects including neuroprotection, antiepileptic, and anti-inflammatory properties
PMID: 35083862
4
GPR55 as cannabinoid receptor gene and its role in pharmacogenetics of cannabinoid therapy
PMID: 28534260
5
CBD affinity for GPR55 and relevance to epilepsy pathophysiology
PMID: 32053110
6
GPR55 distribution and role in glucose homeostasis, obesity, and type 2 diabetes
PMID: 28457969
7
Endocannabinoids as endogenous ligands of GPR55 and metabolism pathways
PMID: 27516570
8
GPR55 activation by palmitoylethanolamide in PPAR-α-independent pathways
PMID: 33114698
Disease Associationsⓘ20
sprainOpen Targets
0.32Weak
preeclampsiaOpen Targets
0.30Weak
psoriatic arthritisOpen Targets
0.29Weak
psoriasisOpen Targets
0.29Weak
fungal infectious diseaseOpen Targets
0.23Weak
prostate cancerOpen Targets
0.11Weak
Familial prostate cancerOpen Targets
0.11Weak
neoplasmOpen Targets
0.10Suggestive
cholangiocarcinomaOpen Targets
0.09Suggestive
atherosclerosisOpen Targets
0.08Suggestive
rheumatoid arthritisOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
AnxietyOpen Targets
0.07Suggestive
non-small cell lung carcinomaOpen Targets
0.07Suggestive
Alzheimer diseaseOpen Targets
0.06Suggestive
glioblastoma multiformeOpen Targets
0.06Suggestive
SepsisOpen Targets
0.06Suggestive
non-alcoholic steatohepatitisOpen Targets
0.05Suggestive
myocardial infarctionOpen Targets
0.05Suggestive
myeloid sarcomaOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GNA13Protein interaction99%GNA12Protein interaction98%MGLLProtein interaction97%NAPEPLDProtein interaction93%GPR119Protein interaction92%ARRB1Protein interaction91%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
62%
Lung
42%
Heart
20%
Liver
17%
Ovary
5%
Gene Interaction Network
Click a node to explore
GPR55GNA13GNA12MGLLNAPEPLDGPR119ARRB1
PROTEIN STRUCTURE
Preparing viewer…
PDB9GE2 · 2.51 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.02LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.62 [0.39–1.02]
RankingsWhere GPR55 stands among ~20K protein-coding genes
  • #3,427of 20,598
    Most Researched135 · top quartile
  • #10,069of 17,882
    Most Constrained (LOEUF)1.02
Genes detectedGPR55
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The Basal Pharmacology of Palmitoylethanolamide.
PMID: 33114698
Int J Mol Sci · 2020
1.00
2
The proposed mechanisms of action of CBD in epilepsy.
PMID: 32053110
Epileptic Disord · 2020
0.90
3
A narrative review of molecular mechanism and therapeutic effect of cannabidiol (CBD).
PMID: 35083862
Basic Clin Pharmacol Toxicol · 2022
0.80
4
Pharmacogenetics of Cannabinoids.
PMID: 28534260
Eur J Drug Metab Pharmacokinet · 2018
0.70
5
Structural basis for lipid-mediated activation of G protein-coupled receptor GPR55.
PMID: 40000629
Nat Commun · 2025
0.60