Systemic acid base homeostasis is tightly regulated by the lung and an elaborate system of transporters in the kidney. OGR1 is a member of a novel subfamily of G-protein coupled receptors that have been identified as proton-sensors. Thus, we tested for the effect of OGR1 on the activity of renal acid-base transporters. In both normal and OGR1 transfected HEK293 cells, reducing pH from 8 to 7.1 resulted in a significant upregulation of Na+ /H+ exchanger (NHE) and vacuolar H+ -ATPase activity which was more pronounced in OGR1 expressing cells. Activation of OGR1 resulted also in an increase in intracellular calcium and the stimulatory effect of OGR1 on NHE activity required PKC and ERK1/2. In isolated proximal tubules from WT and OGR1 KO mice, absence of OGR1, altered regulation of NHE and H+ - ATPase activity by extracellular pH changes. Similarly, we found evidence that OGR1 is involved in the regulation of H+ -ATPases in acid secretory intercalated cells in the collecting duct.Our data suggest that OGR1 is a proton sensing receptor that may be involved in modulating acutely the activity of Na/H exchangers and H+ -ATPases in epithelial cells. The effects of OGR1 are mediated through intracellular calcium, PKC and ERK1/2.