ATP1B1 encodes the β1 subunit of the Na+/K+-ATPase pump, a critical regulator of cellular ion homeostasis and membrane potential across diverse tissues. The protein functions as an obligate component of the heterodiomeric Na+/K+-ATPase complex with the α-subunit ATP1A1, maintaining intracellular sodium and potassium gradients essential for cell survival 1. Beyond its canonical role in ion transport, ATP1B1 participates in establishing epithelial cell polarity and cell adhesion, with localized expression in cochlear hair cells, supporting cells, and spiral ganglion neurons where it supports auditory nerve signaling 2. Emerging evidence reveals ATP1B1's involvement in antiviral innate immunity; upon viral infection, ATP1B1 is upregulated and interacts with TRAF3 and TRAF6 to potentiate their ubiquitination, enhancing interferon and inflammatory cytokine production 3. Additionally, ATP1B1 serves as a fusion partner in oncogenic rearrangements, including ATP1B1-NRG1 and ATP1B1-PRKACA fusions identified in pancreatic and pancreatobiliary cancers, where these fusions constitute therapeutic targets 4, 5, 6. The protein also interacts with human cytomegalovirus UL136 protein, suggesting roles in viral pathogenesis and cellular ion homeostasis during infection 7. Disease associations include cardiovascular disorders, cataracts, and hematologic malignancies, reflecting ATP1B1's tissue-wide importance in maintaining cellular homeostasis.