P-type ATPases are a large family of molecular pumps that exploit a phosphorylated enzyme intermediate in a two-step mechanism of ATP hydrolysis, cycling through states which are associated with ion transport or ion counter-transport. The Na⁺/K⁺-ATPase, a member of this family, is almost exclusively found in animals, although close homologues have been reported in certain archaea, algae and oomycetes.

The Na⁺/K⁺-ATPase is comprised of a nucleotide-binding (N) and phosphorylation (P) domain, a transmembrane core (M1–M6) and a large carboxy-terminal M7–M10 segment. Na⁺/K⁺-ATPase undergoes large conformational changes as part of its functional cycle giving rise to two distinct enzymatic states: E1, which is a high-affinity state for the primary transported ion- Na⁺ and E2, which is the low-affinity state for the Na⁺ ion. The two states arise from the autocatalysed formation and breakdown of a phosphoenzyme intermediate, coupled to the binding, occlusion, translocation and release of ions. The phosphorylation site is the Asp residue of a conserved DKTGT motif. The core of the membrane transport domain encompasses transmembrane helices M1–M6, which hold the main ion-binding sites and are necessary for cytoplasmic and extracellular ion transport. A terminal R domain extension, which serves as a regulatory unit, can be found in the C-terminal of the protein. This unit is auto-inhibitory and is predicted to restrict transmembrane helix movements and/or access of ions to the membrane transport core¹.  

Na⁺/K⁺-ATPase has been implicated in the pathogenesis of Alzheimer’s Disease. A deficiency in several Na⁺/K⁺-ATPase isoform genes induce learning and memory deficits, and the α isoform is altered in Alzheimer’s Disease².