ATP1A1 encodes the catalytic alpha-1 subunit of the Na+/K+-ATPase, a ubiquitous plasma membrane pump that hydrolyzes ATP to exchange intracellular sodium for extracellular potassium 12. This ion exchange establishes the electrochemical gradient essential for cellular homeostasis and membrane potential maintenance across all eukaryotic cells 3. ATP1A1 functions within a conserved molecular network; the human-specific protein SP0535 interacts with ATP1A1 to modulate Src kinase phosphorylation, promoting neuronal proliferation and cortical expansion during brain development 4. ATP1A1 mutations have significant clinical relevance. Somatic mutations in ATP1A1 are identified in approximately half of aldosterone-producing adenomas, contributing to primary aldosteronism—the most common form of secondary hypertension affecting ~10% of hypertensive patients 56. Germline ATP1A1 mutations cause Charcot-Marie-Tooth disease, axonal type 2DD, a hereditary neuromuscular disorder 7. During SARS-CoV-2 infection, ATP1A1 directly binds viral RNAs and represents a host dependency factor; pharmacological inhibition of ATP1A1 reduces viral replication in human cells 8. Additionally, ATP1A1 stabilization through its beta-subunit partner ATP1B1 regulates Na+/K+-ATPase function in acute myeloid leukemia pathogenesis 3. In esophageal squamous cell carcinoma, GPR37-mediated ATP1A1 ubiquitination and degradation inhibits tumor progression and radioresistance 9.