The minimal functional enzyme unit of Na,K-ATPase consists of an α—β complex. The α-subunit bears all functional domains of the enzyme and so far a regulatory role for the β-subunit in the catalytic cycle has not been established. On the other hand, increasing experimental evidence suggests that the β-subunit is an indispensable element for the structural and functional maturation of the enzyme as well as its intracellular transport to the plasma membrane. This brief review summarizes the experimental data supporting the hypothesis that assembly of the β-subunit is needed for the α-subunit to acquire the correct, stable configuration necessary for the acquisition of functional properties and its exit from the ER.