SLC5A2 encodes SGLT2, an electrogenic sodium-glucose cotransporter that actively transports D-glucose with a 1:1 Na+ to glucose coupling ratio 1. This transport is driven by the transmembrane Na+ electrochemical gradient established by the Na+/K+ pump 1. Unlike SGLT1, SGLT2 requires the auxiliary protein MAP17 for full transporter activity 1. SGLT2 mediates reabsorption of the majority of filtered glucose in the kidney's proximal tubules, with SGLT1 reabsorbing the remainder 2. Mutations in SLC5A2 cause familial renal glucosuria, characterized by glucose excretion in urine 2. Clinically, SGLT2 inhibitors (gliflozins) are widely used antidiabetic agents that enhance urinary glucose excretion 23. Beyond glucose lowering, these inhibitors reduce atherosclerotic events, heart failure hospitalizations, and slow chr16 kidney disease progression, making them beneficial even in non-diabetic patients 3. SLC5A2 genetic polymorphisms influence both baseline glucose metabolism and individual response to SGLT2 inhibitor therapy, though current evidence suggests variable clinical significance 4. The pharmacological targeting of SGLT2 represents a mechanistically distinct approach to diabetes management with pleiotropic cardiorenal benefits.