Na+/H+ exchangers (NHE) of mammalian cells are plasma membrane intrinsic proteins mediating exchange of N+ and H+ ions in various tissues. The NHE catalyzes the electroneural transport of extracellular Na+ for intracellular H+. They play a major role in regulation of intracellular pH (pHi) in addition to trans-cellular absorption of Na+, cell volume regulation and possibly in cell proliferation. These primary functions of the Na+/H+ exchanger have been related to many pathophysiological states, including hypertension, organ growth and hypertrophy, and regression of cancer and renal intestinal disorders. Five NHE isoforms (NHE1-5) have been cloned so far. They are all similar in their primary structure and predicted to have 10-12 transmembrane domains. The COOH-terminals of NHE1, NHE2 and NHE3 are intracellular.