In order to function in optimal conditions, cells must maintain a close to neutral intracellular pH. They have adopted various mechanisms in order to do so, one of which is via Na⁺/H⁺ exchangers (NHEs). Genes belonging to this group are expressed along a very broad range of organisms and are essential for protecting cells against intracellular acidification¹.
 
To date, nine genes have been identified in mammals; NHE1-9. These membrane proteins have 10-12 transmembrane domains depending on whether a splice variant is expressed and an intracellular N-terminal. The C-terminal domain can be either intracellular or extracellular, also depending whether a splice variant of the protein is involved. The C-terminal part of the protein also undergoes posttranslational modification such as phosphorylation². Both NHE-1 and NHE-2 have an extracellular loop which is glycosylated^1,3,4.
 
Under physiological conditions, the Na⁺/H⁺ exchanger mediates the exchange of one extracellular Na⁺ ion for one intracellular proton, thereby keeping the overall charge neutral¹. The extracellular binding site of Na⁺ is not selective as it can also bind Li⁺ and H^{+ 1,5,6}.  K⁺ ions inhibit NHE-1 but have no effect on NHE-2⁷. The activation of NHE-1 and NHE-2 is sensitive to intracellular acidic pH. Under physiological conditions, both exchangers are not active and upon a drop of intracellular pH, they are rapidly activated^1,5,8.
 
NHE-1 expression is ubiquitous and may serve as a housekeeping gene⁹.