The sodium pump, or Na+/K+-ATPase (NKA), is a crucial enzyme in all animal cells, responsible for transporting sodium (Na+) and potassium (K+) ions across the cell membrane using energy from ATP hydrolysis. This process creates and maintains an electrochemical gradient, essential for various cellular functions, including cell volume regulation, electrical excitability, and secondary active transport. Despite being discovered decades ago, NKA remains a subject of intense research, with recent studies exploring its structure, function, and interactions with various substances. Beyond its role as a pump, evidence suggests that NKA also functions as a receptor for cardiac glycosides like ouabain, triggering signaling pathways that have significant morphological and physiological effects. This review highlights the latest findings on NKA's role as a pump and its interactions with cardiac glycosides, emphasizing its function in epithelial physiology and its role as a receptor for cardiac glycosides that regulate cell-cell contacts, proliferation, differentiation, and adhesion. The review also discusses the role of NKA β-subunits as cell adhesion molecules in glia and epithelial cells. NKA is classified as a member of the P-type ATPase superfamily, with three subunits: α, β, and FXYD. The α subunit is responsible for the catalytic function, while the β subunit acts as a chaperone and influences NKA's transport properties. The FXYD subunits regulate NKA activity through post-translational modifications. Recent studies have shown that NKA's pumping activity is influenced by various substances, including cardiac glycosides, which can either inhibit or enhance its function. Additionally, NKA's role as a signal-transducing receptor has been explored, with studies showing that CGs can activate various signaling pathways, including SRC/EGFR, RAS/MAPK/ERK, and IP3K/Akt/mTOR. These pathways are involved in fundamental cellular processes, including proliferation, differentiation, apoptosis, and intercellular communication. The review also discusses the role of NKA in various diseases, particularly hypertension and cancer, and highlights the potential therapeutic applications of NKA-related compounds. Overall, the review underscores the multifaceted role of NKA in cellular physiology and its significance in various physiological processes.The sodium pump, or Na+/K+-ATPase (NKA), is a crucial enzyme in all animal cells, responsible for transporting sodium (Na+) and potassium (K+) ions across the cell membrane using energy from ATP hydrolysis. This process creates and maintains an electrochemical gradient, essential for various cellular functions, including cell volume regulation, electrical excitability, and secondary active transport. Despite being discovered decades ago, NKA remains a subject of intense research, with recent studies exploring its structure, function, and interactions with various substances. Beyond its role as a pump, evidence suggests that NKA also functions as a receptor for cardiac glycosides like ouabain, triggering signaling pathways that have significant morphological and physiological effects. This review highlights the latest findings on NKA's role as a pump and its interactions with cardiac glycosides, emphasizing its function in epithelial physiology and its role as a receptor for cardiac glycosides that regulate cell-cell contacts, proliferation, differentiation, and adhesion. The review also discusses the role of NKA β-subunits as cell adhesion molecules in glia and epithelial cells. NKA is classified as a member of the P-type ATPase superfamily, with three subunits: α, β, and FXYD. The α subunit is responsible for the catalytic function, while the β subunit acts as a chaperone and influences NKA's transport properties. The FXYD subunits regulate NKA activity through post-translational modifications. Recent studies have shown that NKA's pumping activity is influenced by various substances, including cardiac glycosides, which can either inhibit or enhance its function. Additionally, NKA's role as a signal-transducing receptor has been explored, with studies showing that CGs can activate various signaling pathways, including SRC/EGFR, RAS/MAPK/ERK, and IP3K/Akt/mTOR. These pathways are involved in fundamental cellular processes, including proliferation, differentiation, apoptosis, and intercellular communication. The review also discusses the role of NKA in various diseases, particularly hypertension and cancer, and highlights the potential therapeutic applications of NKA-related compounds. Overall, the review underscores the multifaceted role of NKA in cellular physiology and its significance in various physiological processes.