Na⁺-K⁺ ATPase or Na-pump ATPase, a member of “P”-type ATPase superfamily, is characterized by association of multiple isoforms mainly of it’s α- and β- subunits. At present four different α- (α-1,α-2,α-3 and α-4) and three β- (β-1, β-2, and β-3) isoforms have been identified in mammalian cells and their differential expressions are tissue specific. Regulation of Na⁺-K⁺ ATPase activity is an important but a complex process, which involves short-term and long-term mechanisms. Short-term regulation of Na⁺-K⁺ ATPase is either mediated by changes in intracellular Na⁺ concentrations that directly affect the Na⁺-pump activity or by phosphorylation/dephosphorylation-mediated by some stimulants leading to changes in its expression ... Read moreand transport properties. On the other hand, long-term regulation of Na⁺-K⁺ ATPase is mediated by hormones, such as mineralocorticoids and thyroid hormones, which cause changes in the transcription of genes of α- and β- subunits leading to an increased expression in the level of Na⁺-pump. Several studies have revealed a relatively new type of regulation that involves the association of small, single span membrane proteins with this enzyme. These proteins belong to the FXYD family, the members of which share a common signature sequence encompassing the transmembra