{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC5A2 encodes the sodium‐glucose cotransporter 2 (SGLT2), a membrane protein predominantly expressed in the apical domain of renal proximal tubule cells where it is responsible for reabsorbing approximately 90% of the filtered glucose via a sodium‐dependent mechanism. Its high‐capacity, low‐affinity transport of glucose is characterized by a strict 1:1 stoichiometry for Na⁺ and glucose, and its activity is finely tuned by cellular signaling pathways, including phosphorylation events. Notably, naturally occurring mutations in SLC5A2 cause familial renal glucosuria, where defects in SGLT2 function lead to inappropriate urinary glucose excretion despite normal plasma glucose levels—findings that have been confirmed in several family studies with variable inheritance patterns and phenotypic severity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical renal role, SLC5A2 expression has been detected in extrarenal tissues—including in pancreatic islet alpha cells, where it appears to modulate glucagon secretion and may contribute to altered hormone release in diabetes. Variations in SLC5A2 genetic makeup influence glycemic phenotypes in type 2 diabetes, and emerging evidence points to its involvement in the metabolic reprogramming of certain cancers and even in the choroid plexus of the brain, suggesting additional roles in non‐renal glucose uptake and as a potential diagnostic marker."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPharmacological inhibition of SGLT2 by gliflozins effectively induces glycosuria and elicits a cascade of metabolic adaptations—including enhanced endogenous glucose production, a shift from carbohydrate to lipid oxidation, and increased ketone body formation—that contribute to improved glycemic control and cardioprotective and renoprotective outcomes in patients with type 2 diabetes. In parallel, detailed biophysical and molecular evaluations have demonstrated that SGLT2’s transport kinetics and regulatory properties are altered in disease states, emphasizing its dual utility as both a therapeutic target and a biomarker in diabetes and its complications."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "16"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "René Santer, Martina Kinner, Christoph L Lassen, et al. 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