Glucose Transporters: Structure, Trafficking, Physiology, and Disease Relevance

Glucose transport across biological membranes in mammals depends primarily on two transporter families: the facilitative glucose transporters of the SLC2 family and the sodium-dependent cotransporters of the SLC5 family. Together, these proteins mediate tissue-specific glucose uptake, epithelial absorption and reabsorption, nutrient sensing, and adaptive responses to metabolic stress. This review summarizes current knowledge of transporter classification, structural mechanism, tissue distribution, intracellular trafficking, and disease associations, with emphasis on GLUT1, GLUT2, GLUT3, GLUT4, SGLT1, and SGLT2. It also discusses less well-characterized members of the extended GLUT family, the therapeutic implications of SGLT inhibition, and unresolved questions regarding transporter specificity. Furthermore, the review integrates emerging evidence on CAR-T cell engineering, Alport syndrome, lupus nephritis, erythropoietic responses, and the reduction in dementia risk associated with transporter modulation.