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 (By similarity). 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. Expressed in kidney. Expressed in uterus and endometrial epithelial cells. Expressed in the inner segments of inner medullary collecting ducts (IMCD) in kidney. May be phosphorylated. Mice survive and appear outwardly normal. Analysis of their stomach contents reveals that mice are hypochlorhydric. Their gastric mucosa reveal an sharply reduced numbers of parietal cell, a loss of mature chief cells, an increased numbers of mucous and undifferentiation cells and an increase in the number of necrotic and apoptotic cells. Parietal cells exhibit limited development of canalicular membranes and a virtual absence of tubulovesicles and some of the microvilli had centrally bundled actin. 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.