FXYD3: A Key Regulator of Ion Homeostasis and Redox Balance inCancer Biology

Cancer continues to be a major health burden, with millions of new cases and deaths reported annually, and metastasis remains the leading cause of cancer-related mortality. Disruption of transmembrane proteins is a major regulator of tumor development and progression. This review highlights FXYD3, a single-transmembrane protein that regulates Na+ /K+ -ATPase activity and functions in maintaining ion balance, redox homeostasis, and proliferative signaling in both cancer stem cells and bulk tumor populations. Its expression varies across various cancers, such as breast, pancreatic, lung, colorectal, gastric, and endometrial cancer, where it is linked with tumor development, therapy resistance, and immune modulation. Its involvement in pathways such as PI3K-AKT and cGMP-PKG contributes to malignancy. It protects cells from oxidative stress, thereby promoting cell survival and inhibiting apoptosis. Accumulating evidence highlights the potential role of FXYD3 as an emerging biomarker with relevance to diagnosis, prognosis, and therapeutics. This review provides an overview of FXYD3's role in cancer biology from translational relevance to its potential as a diagnostic, prognostic, and therapeutic target.