Sodium/potassium-transporting ATPase subunit alpha-3

ATP1A3 encodes the catalytic alpha-3 subunit of the Na+/K+-ATPase, which catalyzes ATP-dependent exchange of sodium and potassium ions across the plasma membrane to establish the electrochemical gradients essential for neuronal excitability and active nutrient transport (UniProt: P13637). The protein is widely expressed and particularly critical in the nervous system for maintaining neuronal ion homeostasis.

ATP1A3 mutations cause several neurodevelopmental and neurological disorders including Dystonia 12, Alternating Hemiplegia of Childhood 2, cerebellar ataxia syndromes, and Developmental and Epileptic Encephalopathy 99 (UniProt: P13637), reflecting its essential role in neuronal function. These genetic associations underscore the protein's importance in maintaining proper neurological homeostasis.

In Alzheimer's disease, ATP1A3 is upregulated in post-mortem AD brain relative to age-matched controls (mean log2FC = 0.648, Chaparral AD proteomics). This elevation may reflect compensatory responses to neuronal stress or altered ion homeostasis in AD pathology, potentially linking metabolic dysregulation to AD neurodegeneration.