Ion channels are multimeric proteins located in the plasma membrane that play a critical role in the regulation of cellular processes¹. The gradient of sodium (Na⁺) and potassium (K⁺) across the plasma membrane is regulated by the Na⁺/K⁺-ATPase enzyme complex. Na/K-ATPase hydrolyzes one ATP molecule in order to pump three Na⁺ ions out of the cell and two K⁺ ions into the cell during every pumping cycle. Na⁺/K⁺-ATPase activity is vital for sodium and potassium homeostasis in cells, which are important for numerous enzymatic functions and secondary transport of different molecules². 

Na⁺/K⁺-ATPase is a heteromeric transmembrane protein complex consisting of α- and β-subunits and a regulatory subunit belonging to the FXYD proteins. The catalytic α-subunit is responsible for transport activities and contain 10 transmembrane domains (TMDs). The β-subunit is heavily glycosylated and function as a molecular chaperone. The association of the β-subunit increases the stability of the catalytic α-subunit and dictates the affinity toward sodium and potassium. In addition, the β-subunit is necessary for the complex migration into the plasma membrane³.

β-subunits has three different isoforms β-1, β-2 and β-3 that consist of small N-terminal (30-AA), a TM helix and large C-terminal (240-AA) with different tissue specificities. β-1 found to have additional role in the response of cells to oxidative stress via glutathionylation of a cysteine residue located at the center of the TMD, the same cysteine is absent in the other beta subunits⁴.