Hyperglycemia-induced intracellular calcium overload activates calcium-dependent proteases (e.g., calpain) and TRPC6 channels, leading to mesangial extracellular matrix deposition and podocyte cytoskeletal collapse, which exacerbate proteinuria and glomerulosclerosis (1, 2, 8–13, 19). The gene discussed is TRPC6; the disease is Hyperglycemia.