ATP1A3 encodes the alpha-3 subunit of the Na+/K+-ATPase, a catalytic enzyme that hydrolyzes ATP to pump sodium and potassium ions across the plasma membrane, establishing essential electrochemical gradients for neuronal function 1. This sodium-potassium gradient drives active transport of nutrients and maintains neuronal excitability, with ATP1A3 particularly abundant in neuron-derived extracellular vesicles 2. Mutations in ATP1A3 cause a broad neurological disease spectrum characterized by paroxysmal events, hyperkinesia, cognitive impairment, and neuropsychiatric symptoms 3. The most well-defined conditions include alternating hemiplegia of childhood (70% of cases), rapid-onset dystonia-parkinsonism, and cerebellar ataxia with sensorineural hearing loss 4. Heterozygous mutations are also associated with early infantile epileptic encephalopathy, often featuring polymicrogyria and severe developmental impairment, indicating that impaired Na+/K+-ATPase function disrupts normal brain morphogenesis 1. ATP1A3-related hyperkinetic movement disorders frequently present with generalized chorea and dystonia in early childhood 5. Additionally, ATP1A3 variants contribute to auditory neuropathy and infantile migrating focal seizures 6, 7. Clinically, prime editing approaches have successfully corrected ATP1A3 mutations in mouse models, rescuing ATPase activity and improving paroxysmal spells, motor deficits, and lifespan, offering potential therapeutic strategies 8.