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 (PubMed:26358773). Plays an important role in signal transduction. Binds SLC9A3R1 and SLC9A3R2. Interacts with CHP1, CHP2 and SHANK2. Interacts with PDZK1 (via C-terminal PDZ domain) (By similarity). Interacts with PDZD3 and interactions decrease in response to elevated calcium ion levels. Interacts with AHCYL1; the interaction is required for SLC9A3 activity (PubMed:18829453, PubMed:20584908). In intestinal epithelial cells, localizes to the ileal brush border. Phosphorylation at Ser-663 by SGK1 is associated with increased abundance at the cell membrane. Angiotensin-2 enhances apical expression (By similarity). Phosphorylated by PKA, which inhibits activity. Phosphorylation at Ser-663 by SGK1 is associated with increased abundance at the cell membrane. The disease is caused by variants affecting the gene represented in this entry. 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.