Proton-sensing G-protein coupled receptor couples to multiple intracellular signaling pathways, including GNAS/cAMP, GNAQ/phospholipase C (PLC), and GNA13/Rho pathways. Acidosis-induced GPR4 activation increases paracellular gap formation and permeability of vascular endothelial cells through the GNA12/GNA13/Rho GTPase signaling pathway. In the brain may mediate central respiratory sensitivity to CO(2)/H(+). Belongs to the G-protein coupled receptor 1 family.