GPR68

Proton-sensing G protein-coupled receptor activated by extracellular pH, which is required to monitor pH changes and generate adaptive reactions. The receptor is almost silent at pH 7.8 but fully activated at pH 6.8. 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 phospholipase C. GPR68 is mainly coupled to G(q) G proteins and mediates production of diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Acts as a key mechanosensor of fluid shear stress and membrane stretch. Expressed in endothelial cells of small-diameter resistance arteries, where it mediates flow-induced dilation in response to shear stress. May represents an osteoblastic pH sensor regulating cell-mediated responses to acidosis in bone (By similarity). Acts as a regulator of calcium-sensing receptor CASR in a seesaw manner: GPR68-mediated signaling inhibits CASR signaling in response to protons, while CASR inhibits GPR68 in presence of extracellular calcium (By similarity)..

Function from UniProtKB (Q15743), read 2026-09-23. CC BY 4.0.