GPR65

Proton-sensing G protein-coupled receptor activated by extracellular pH, which is required to monitor pH changes and generate adaptive reactions. Activated by an optimal pH of 7.4. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase. GPR65 is mainly coupled to G(s) G proteins and mediates activation of adenylate cyclase activity. May also act as a receptor for the glycosphingolipid psychosine (PSY) and several related glycosphingolipids. Plays a role in immune response by maintaining lysosome function and regulating T-cell metabolism. Acts as a regulator of inflammation by mediating pH-sensing of extracellular acidification which takes place in inflamed tissues: activation regulates endo-lysosomal function of immune cells and T-cell metabolism (By similarity). Constitutively active in endosomes and stimulates adenylate cyclase production from endosomes independently from extracellular pH changes..

Function from UniProtKB (Q8IYL9), read 2026-09-23. CC BY 4.0.