SLC8B1 encodes NCLX, the mitochondrial sodium/calcium antiporter that mediates the exchange of 3 sodium ions per 1 calcium ion to extrude calcium from mitochondria. This exchanger is essential for mitochondrial calcium homeostasis and cell survival, particularly in cardiomyocytes. NCLX regulates glucose-dependent insulin secretion in pancreatic beta-cells by controlling calcium efflux during the first phase of insulin secretion, and is required for store-operated calcium entry by modulating mitochondrial redox status 12. Recent structural studies reveal that NCLX functions as a H+/Ca2+ exchanger rather than exclusively as a Na+/Ca2+ exchanger 3. In cardiac physiology, NCLX prevents mitochondrial calcium overload and associated oxidative stress; deletion of Slc8b1 in adult mouse hearts causes sudden death and fulminant heart failure within 14 days, whereas NCLX overexpression protects against ischemia-induced cardiomyocyte necrosis 4. NCLX also participates in hypoxic responses by regulating mitochondrial electron transport chain function and reactive oxygen species production, linking acute and medium-term hypoxic adaptation 56. In colorectal cancer, calcium extrusion-related genes including SLC8B1 were identified as part of a prognostic signature associated with poor patient outcomes 7.