Proton-sensing G protein-coupled receptor activated by extracellular pH, which is required to monitor pH changes and generate adaptive reactions (PubMed:15326175, PubMed:15618224, PubMed:20855608, PubMed:33478938, PubMed:37722051, PubMed:39753132, PubMed:40211064). Activated by an optimal pH of 7.4 (PubMed:39753132). 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 (PubMed:15326175, PubMed:15618224, PubMed:37722051, PubMed:39753132). GPR65 is mainly coupled to G(s) G proteins and mediates activation of adenylate cyclase activity (PubMed:15618224, PubMed:37722051, PubMed:39753132). May also act as a receptor for the glycosphingolipid psychosine (PSY) and several related glycosphingolipids (PubMed:11309421, PubMed:15326175). Plays a role in immune response by maintaining lysosome function and regulating T-cell metabolism (PubMed:27287411). 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 (PubMed:39753132). {ECO:0000250|UniProtKB:Q61038, ECO:0000269|PubMed:11309421, ECO:0000269|PubMed:15326175, ECO:0000269|PubMed:15618224, ECO:0000269|PubMed:20855608, ECO:0000269|PubMed:27287411, ECO:0000269|PubMed:33478938, ECO:0000269|PubMed:37722051, ECO:0000269|PubMed:39753132, ECO:0000269|PubMed:40211064}. This is the function of GPR65 (G protein-coupled receptor 65, Ensembl gene identifier ENSG00000140030).