Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction. Detected in early distal renal tubules in the kidney bundle zone, in proximal and late distal tubules in the kidney sinus zone, in absorptive epithelial cells of the intestine and in rectal epithelium (at protein level). Isoform 1 is expressed strongly in the gills, at intermediate levels in the kidney, spleen, rectum, spiral intestine and skin, and weakly in the brain, blood and rectal gland. Isoform 2 is expressed strongly in the kidney, rectum and spiral intestine, and weakly in muscles and the rectal gland. High salinity induces expression of isoform 2 in the kidney; conversely, low salinity induces expression in the intestine. Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family. The number, localization and denomination of hydrophobic domains in the Na(+)/H(+) exchangers vary among authors.