Major, functionally relevant features of Na+/K+-ATPase are located on the alpha-subunit of the alphabeta-heterodimer. They include the binding sites for the transported cations, the binding pocket and phosporylation site for ATP as well as regulatory phosphorylation sites for protein kinases, sensitivity for cardiac glycosides and isoform specificity. These regions of the alpha-subunit are reviewed, and structure-function relationships are discussed. The discussion is based on electrophysiological data that were obtained from Xenopus oocytes with only endogenous pumps or with expressed pumps from other species or pumps that were genetically modified.