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.

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.