Sodium-Potassium ATPase in cardiovascular diseases: Insights into structure, function, and therapeutic targets

The sodium/potassium adenosine triphosphatase (Na⁺/K⁺ ATPase, NKA) is a ubiquitous membrane protein crucial for maintaining ionic homeostasis by regulating Na⁺ and K⁺ concentrations across the plasma membrane. Emerging evidence indicates that NKA plays a multifaceted role in cardiovascular physiology and pathophysiology beyond its well-established ion-transporting functions. Dysregulation of NKA function has been increasingly linked to cardiovascular diseases such as heart failure, hypertension, and arrhythmias. While the fundamental biological roles of NKA are well-documented, its precise contributions to cardiovascular disease pathogenesis and therapeutic potential remain insufficiently explored. This review provides a comprehensive overview of the molecular structure and subunit composition of NKA, highlighting the assembly of its subunits into a functionally active complex. We outline the fundamental roles of NKA, emphasizing its functions, expression profiles, and subcellular localization within the cardiovascular system. Additionally, we examine the alterations in NKA activity and subunit expression associated with cardiovascular diseases, and their impact on disease progression. Notably, we highlight the emerging therapeutic potential of targeting NKA activation sites, particularly through antibody-based approaches, as a novel strategy for treating cardiovascular diseases. Finally, we discuss key challenges and propose future research directions in NKA biology, aiming to deepen our understanding of its role in cardiovascular health and facilitate the development of novel therapeutic strategies.