The cell-surface expression of the Na+/K+-ATPase is tightly regulated at the ER/Golgi transit level. The assembly of the alpha- and beta-subunits is a prerequisite for the maturation of the enzyme and its exit from the ER. At present, the fate of the functional ATPase, once it reaches the plasma membrane, is obscure, although endocytosis, recycling, and degradation in the lysosome are known to be involved. In this study, we shall demonstrate the differential degradation of the Na+/K+-ATPase subunits in the plasma membrane: that is, lysosomal degradation of alpha-subunits and proteasomal degradation of beta-subunits, and propose the possibility of the subunit dissociation in the plasma membrane.