Mammalian NHE (Na+/H+ Exchanger) is an integral membrane protein that is known to regulate intracellular pH by removing a proton in exchange for an extracellular sodium ion. There are nine known isofoms of NHE. The best characterized is NHE1, involved not only in intracellular pH control, but cell-volume control, cytoskeletal organization, heart disease and cancer. Transport by the NHE plays a pivotal role in the damage caused to the human myocardium during and following a myocardial infarction, and it is considered to represent a key step in the oncogenic transformation of cancerous cells. NHE comprises an N-terminal membrane domain that transports ions, and a C-terminal cytoplasmic domain that regulates activity and mediates cytoskeletal interactions. NHE2 - NHE5 isoforms are localized to the plasma membrane but exhibit greater tissue- specificity. NH2 and NH3 are more highly expressed in the kidney and intestine. Structurally, a single transmembrane segment from NHE1 has been solved, and the structure of bacterial Na+/H+ antiporter NhaA has been elucidated.