Na,K-ATPase activity is critical for maintaining electrogenesis, contractile function and skeletal muscle performance. This review is devoted to the analysis of the results of recent studies in the field of molecular and functional diversity of Na,K-ATPase in skeletal muscles, which co-express alpha 1 and alpha 2 isoforms of the catalytic and transport Na,K-ATPase alpha subunit. The issues that seem to be most promising in terms of their further development are considered. The available facts indicate that, in contrast to the alpha 1 isoform that demonstrates functional stability, the alpha 2 isoform is distinguished by a high degree of plasticity, which is due to its specific membrane localization, functional and molecular interactions with the protein and lipid environment, as well as the peculiarities of its regulation by various factors. Functional disorders of the Na,K-ATPase alpha 2 isoform are among the most common signs characteristic of both chronic and short-term forms of motor dysfunction.