Table 1.

NHE expression, localization, and (proposed) function

Isoform	Location		Proposed Function(s)	References
	Tissue*	Cellular
NHE1	Ubiquitous	Plasma membrane (basolateral membrane in epithelia)	Cell volume and intracellular pH regulation	5, 92, 95, 104, 105
NHE2	Gastrointestinal tract, kidney, brain, uterus/testis	Plasma membrane (apical membrane in epithelia)	Glandular secretory processes, minor role in intestinal Na+ and water absorption?	25, 28, 98, 108
NHE3	Gastrointestinal tract, kidney, gallbladder, epididymis	Plasma membrane (apical), recycling endosomes	Intravascular volume homeostasis, pH regulation, Ca2+ homeostasis	17, 18, 96, 97, 109
NHE4	Stomach (kidney and brain)	Plasma membrane (basolateral membrane in epithelia)	Acid extrusion into the stomach, renal ammonia handling	21, 45, 96, 99
NHE5	Brain (neurons)	Plasma membrane and recycling endosomes/synaptic vesicles	Regulation of dentritic spine growth?	11, 33
NHE6	Ubiquitous	Recycling endosomes	Regulation of luminal pH?	24, 81, 89, 95
NHE7	Ubiquitous	trans-Golgi network and endosomes	Regulation of luminal pH in endosomes and/or Golgi?	89, 94, 95
NHE8†	Ubiquitous	Endomembrane (and apical plasma membrane)	Regulation of luminal pH? Role in intravascular pH and volume regulation?	12, 14, 53, 89, 126
NHE9	Ubiquitous	Late endosomes	Regulation of luminal pH?	89

NHE, Na⁺/H⁺ exchanger.

^*The predominant tissue expression is listed only, i.e., this is not an exhaustive list.

^†The NHE family can be divided into plasma membrane isoforms (NHE1–NHE5) and endomembrane isoforms (NHE6–NHE9). NHE8, although predominantly endomembrane, localizes to the plasma membrane in some cell types.