Recently, the proton-activated G-protein coupled receptor OGR1 has been identified as a putative proton-sensor; however the physiological role of this receptor has remained elusive to date. Here we tested for a potential role of OGR1 in acid-base and electrolyte homeostasis. Real-time PCR and immunohistochemistry showed expression of OGR1 in several kidney nephron segments. Intracellular pH measurements demonstrated that OGR1 stimulates Na+/H+-exchanger NHE3 in transfected cells without altering its surface expression. In addition we started to characterize the phenotype of OGR1 KO mice. OGR1 KO grow normally and show no gross abnormalities. On a normal diet, food and water intake, urine exretion and blood parameters revealed no significant difference between the KO and WT mice. Urine and blood pH, and HCO3 levels were within the normal range. However, compared with the WT mice, urinary excretion of potassium and calcium were significantly increased. In contrast magnesium excretion is strongly reduced. Taken together, these data suggest that OGR1 may be involved in local pH control and regulation of electrolyte balance.