GCG encodes proglucagon, which is processed into multiple bioactive peptides including glucagon and glucagon-like peptide-1 (GLP-1) that play critical roles in glucose and energy homeostasis 1. The gene is expressed in pancreatic α-cells, intestinal L-cells, and specific brainstem neurons 1. Glucagon functions as a counterregulatory hormone that increases glucose production during hypoglycemic challenges to restore euglycemia 1. Recent studies demonstrate that glucagon also regulates energy expenditure, with glucagon receptor activation enhancing metabolic effects when combined with GLP-1 and GIP receptor agonists 2. GCG expression varies along the intestinal tract, with both small and large intestine serving as sites of GLP-1 secretion 3. Therapeutically, multi-receptor agonists targeting glucagon receptors alongside GLP-1 and GIP receptors show superior weight loss and glycemic control compared to single-target approaches 45. Additionally, GCG expression in pancreatic α-cells can be modulated by factors like serotonin, which suppresses Gcg expression while promoting α-to-β cell transdifferentiation 6. The retention of glucagon function appears essential for maximizing metabolic benefits in obesity and diabetes treatments 7.