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. May play a specialized role in the kidney in rectifying cell volume in response to extreme fluctuations of hyperosmolar-stimulated cell shrinkage. Is relatively amiloride and ethylisopropylamiloride (EIPA) insensitive. Can be activated under conditions of hyperosmolar-induced cell shrinkage in a sustained intracellular acidification-dependence manner. Activated by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) in a sustained intracellular acidification-dependence manner. Affects potassium/proton exchange as well as sodium/proton and lithium/proton exchange. In basolateral cell membrane, participates in homeostatic control of intracellular pH, and may play a role in proton extrusion in order to achieve transepithelial HCO3(-) secretion. In apical cell membrane may be involved in mediating sodium absorption. Requires for normal levels of gastric acid secretion, secretory membrane development, parietal cell maturation and/or differentiation and at least secondarily for chief cell differentiation. Interacts with CHP1 and CHP2. Enrichment at apical or basolateral membrane may be tissue-dependent. Most abundant in stomach, followed by colon. Lesser amounts were found in kidney, liver, brain, uterus and skeletal muscle. Predominantly expressed in the inner segments of inner medullary collecting ducts (IMCD) in kidney. Highly expressed in the cavi amnoni fields of hippocampus. Expressed in pancreas. Expressed in multiple nephron segments including proximla tubules, medullar thick ascending limbs (MTAL), cortical thick ascending limbs (CTAL), distal covoluted tubules and cortical and medullary collecting ducts. Expressed in submandibular gland. May be phosphorylated. 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.