ATP1B2 is the β2 subunit of the Na+/K+-ATPase holoenzyme, functioning as a critical regulator of ion homeostasis and cellular adhesion. Mechanistically, ATP1B2 mediates intracellular sodium and potassium ion homeostasis 1 and serves as a binding partner for retinoschisin, anchoring this protein to plasma membranes in retinal cells 2. The interaction occurs through a specific protein-protein interaction patch involving threonine 240 in ATP1B2 3. ATP1B2 is essential for cochlear and vestibular K+ cycling, maintaining the endocochlear potential necessary for sensory transduction 1. Disease relevance: ATP1B2 mutations cause spongy degeneration with cerebellar ataxia (SDCA2), a neurodegenerative disorder characterized by cerebellar dysfunction 4. Elevated ATP1B2 expression correlates with poor prognosis in esophageal squamous cell carcinoma and glioblastoma, promoting cancer cell migration and inhibiting apoptosis 56. ATP1B2 also participates in adipogenesis and glucose metabolism regulation in beige adipocytes 7. Clinical significance: ATP1B2 represents a therapeutic target for cancer treatment; selective targeting avoids cardiotoxicity associated with non-selective Na+/K+-ATPase inhibitors since ATP1B2 is minimally expressed in cardiac tissue 6. The Na+/K+-ATPase inhibitor ouabain suppresses ATP1B2-mediated cancer progression 5.