Proton-sensing G-protein coupled receptor couples to multiple intracellular signaling pathways, including GNAS/cAMP, GNAQ/phospholipase C (PLC), and GNA12/GNA13/Rho pathways (PubMed:17145776). Acidosis-induced GPR4 activation increases paracellular gap formation and permeability of vascular endothelial cells through the GNA12/GNA13/Rho GTPase signaling pathway (PubMed:32058960). In the brain may mediate central respiratory sensitivity to CO(2)/H(+) (PubMed:26068853). Detected in neurons of the brain-stem retrotrapezoid nucleus (RTN). Deficient mice display partial neonatal and postnatal lethality, hemorrhages, impaired association of vascular smooth muscle cells with capillaries and small arteries and veins, and impaired contact between mesangial cells and renal glomerular capillaries (PubMed:17145776). The inflammatory response is reduced in an inflammatory hindlimb ischemia-reperfusion model (PubMed:26068853). Deficient mice display reduced central respiratory chemoreflex, increased apnea frequency, and blunted ventilatory responses to CO2 (PubMed:32058960). Belongs to the G-protein coupled receptor 1 family.