FXYD5 (dysadherin) is a membrane-associated regulator of the sodium/potassium-ATPase (NKA) that modulates ion homeostasis and cell adhesion. Structurally, FXYD5 interacts with NKA through its transmembrane domain to increase pump Vmax and enhance sodium export activity 1. Beyond ion transport regulation, FXYD5 promotes epithelial-mesenchymal transition (EMT) by downregulating E-cadherin, reducing cell-cell adhesion and facilitating metastasis 2. FXYD5 expression is significantly elevated in metastatic tumors compared to primary tumors and correlates with cancer progression. In gastric cancer, FXYD5 silencing inhibits invasion, metastasis, and chemotherapy resistance to doxorubicin and vincristine 2. In pancreatic cancer, the USP11/RALY/FXYD5 axis promotes aerobic glycolysis and tumor growth 3, while miR-1180-mediated FXYD5 suppression reduces migration and invasion 4. FXYD5 is dysregulated across multiple cancer types including gastric, colorectal, and pancreatic cancers, and emerging evidence identifies it as a therapeutic target. Its role extends to inflammatory conditions, with FXYD5 identified as an acute pancreatitis-specific gene signature 5. Clinically, FXYD5 represents a potential biomarker and therapeutic target for cancer metastasis and chemotherapy resistance.