FUNCTION Endosomal Na(+), K(+)/H(+) antiporter (PubMed:15522866, PubMed:28635961, PubMed:31676550, PubMed:32277048). Mediates the electroneutral exchange of endosomal luminal H(+) for a cytosolic Na(+) or K(+). By facilitating proton efflux, SLC9A6 counteracts the acidity generated by vacuolar (V)-ATPase, thereby limiting luminal acidification. Responsible for alkalizing and maintaining the endosomal pH, and consequently in, e.g., endosome maturation and trafficking of recycling endosomal cargo (PubMed:15522866, PubMed:28635961, PubMed:31676550, PubMed:32277048). Plays a critical role during neurodevelopment by regulating synaptic development and plasticity (By similarity). Implicated in the maintenance of cell polarity in a manner that is dependent on its ability to modulate intravesicular pH (PubMed:20130086). Regulates intracelular pH in some specialized cells, osteoclasts and stereocilia where this transporter localizes to the plasma membrane (By similarity).CATALYTIC ACTIVITY Na(+)(in) + H(+)(out) = Na(+)(out) + H(+)(in)CATALYTIC ACTIVITY K(+)(in) + H(+)(out) = K(+)(out) + H(+)(in)SUBUNIT Homodimer (PubMed:30296617, PubMed:32277048). Interacts with RACK1; regulates the distribution of SLC9A6 between endosomes and the plasma membrane (PubMed:18057008, PubMed:28635961).INTERACTION Present predominantly in the recycling compartments including early and recycling endosomes, but undergoes plasma membrane localization during vesicular recycling, which is enhanced upon certain stimuli, such as hypoxia (PubMed:11940519, PubMed:28635961, PubMed:30296617). Has a major plasmalemmal distribution in a few specialized cells, such as in vestibular hair bundles and osteoblasts (By similarity).ALTERNATIVE PRODUCTS Ubiquitous. High expression in brain, skeletal muscle, and heart, but is also detected at lower levels in most other tissues.PTM Ubiquitinated (in vitro).PTM Glycosylated.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.CAUTION Was originally (PubMed:9507001) identified as a mitochondrial inner membrane protein, but was later shown to be localized in early and recycling endosomes and not mitochondria (PubMed:11641397, PubMed:11940519).