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. Binds SLC9A3R1 and SLC9A3R2. Interacts with PDZD3 and interactions decrease in response to elevated calcium ion levels. Interacts with PDZK1 (via C-terminal PDZ domain) (By similarity). Interacts with CHP1, CHP2 and SHANK2 (PubMed:12576672, PubMed:16293618). Interacts with AHCYL1; the interaction is required for SLC9A3 activity (PubMed:20584908). In intestinal epithelial cells, localizes to the ileal brush border. Phosphorylation at Ser-661 by SGK1 is associated with increased abundance at the cell membrane. Angiotensin-2 enhances apical expression (By similarity). Most abundant in colon and small intestine, followed by kidney and stomach. In kidney, expressed in proximal tubules and outer medulla (at protein level) (PubMed:20584908). Phosphorylated by PKA, which inhibits activity (PubMed:9933588). Phosphorylation at Ser-661 by SGK1 is associated with increased abundance at the cell membrane (By similarity). 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.