Sodium-glucose transporter 2 (SGLT2) encoded by the SLC5A2 gene, is localized on the brush border membrane of renal proximal tubules and mediates the reabsorption of approximately 90% of glucose filtered by the glomeruli. It serves as the molecular basis for familial renal glucosuria (FRG). SGLT2 inhibitors have been widely used to treat diabetes, diabetic nephropathy, chronic kidney disease, and other conditions. The 17 kDa membrane-associated protein (MAP17) regulates SGLT2 function, and mutations in the gene encoding MAP17 can lead to FRG. Investigations into genotype-phenotype correlations in FRG patients and the structural biology of SGLT2 are critical for understanding its physiological mechanisms and pharmacological actions of SGLT2 inhibitors. This review summarizes current knowledge on genotype-phenotype relationships in FRG, advances in SGLT2 protein structure research, and MAP17-mediated regulation of SGLT2. These insights elucidate SGLT2's physiological roles and provide a theoretical foundation for optimizing clinical applications of SGLT2 inhibitors.

Sodium-glucose transporter 2 (SGLT2) encoded by the SLC5A2 gene, is localized on the brush border membrane of renal proximal tubules and mediates the reabsorption of approximately 90% of glucose filtered by the glomeruli. It serves as the molecular basis for familial renal glucosuria (FRG). SGLT2 inhibitors have been widely used to treat diabetes, diabetic nephropathy, chronic kidney disease, and other conditions. The 17 kDa membrane-associated protein (MAP17) regulates SGLT2 function, and mutations in the gene encoding MAP17 can lead to FRG. Investigations into genotype-phenotype correlations in FRG patients and the structural biology of SGLT2 are critical for understanding its physiological mechanisms and pharmacological actions of SGLT2 inhibitors. This review summarizes current knowledge on genotype-phenotype relationships in FRG, advances in SGLT2 protein structure research, and MAP17-mediated regulation of SGLT2. These insights elucidate SGLT2's physiological roles and provide a theoretical foundation for optimizing clinical applications of SGLT2 inhibitors.