GPR18

G protein-coupled receptor (GPCR) that plays a role in diverse physiological processes particularly within the immune and nervous systems. Becomes active when triggered by various endogenous ligands including endocannabinoid N-arachidonyl glycine (NAGly), delta-9-tetrahydrocannabinol or resolvin D2/RvD2 derived from the omega-3 fatty acid docosahexaenoic acid (DHA). Upon RvD2 binding, facilitates the resolution of inflammation, aiding in tissue repair and homeostasis. Mechanistically, RvD2 ligation initiates Galphas protein coupling, activation of cAMP-PKA signaling pathway and phosphorylation of STAT3, leading to RvD2-stimulated macrophage phagocytosis. Mediates NAGly-induced process of reorganization of actin filaments and induction of acrosomal exocytosis. Activation by N-arachidonoyl glycine (NAGly) can also induce apoptosis in macrophages (By similarity). Plays a role in homeostasis of CD8+ subsets of intraepithelial lymphocytes (IELs) (CD8alphaalpha and CD8alphabeta IELs) in small intestine by supporting preferential migration of CD8alphaalpha T-cells to intraepithelial compartment over lamina propria compartment, and by mediating their reconstitution into small intestine after bone marrow transplant (By similarity). Also participates in hypotensive responses, mediating reduction in intraocular and blood pressure (By similarity)..

Function from UniProtKB (Q14330), read 2026-09-23. CC BY 4.0.