GCGR (glucagon receptor) is a G-protein coupled receptor that serves as the primary regulator of blood glucose homeostasis and glucose production in the liver 1. Upon ligand binding, GCGR undergoes conformational changes that activate downstream signaling cascades, primarily through adenylate cyclase-modulating pathways that increase cAMP production 2. GCGR also engages phosphatidylinositol-calcium signaling systems. The receptor mediates hepatic glycogen hydrolysis and gluconeogenesis in response to fasting and nutrient deprivation, forming a critical liver-alpha cell axis with pancreatic alpha cells 1. Beyond glucose metabolism, GCGR regulates hepatic protein and lipid metabolism 1. Recent studies demonstrate that hepatic ALKBH5 orchestrates glucose and lipid homeostasis by integrating GCGR and mTORC1 signaling pathways, with GCGR inhibition reducing glucose production and improving metabolic dysfunction 2. GCGR activation increases energy expenditure and reduces food intake when co-activated with GLP-1R 3. Clinically, GCGR dysfunction is associated with Mahvash disease and metabolic disorders including type 2 diabetes and fatty liver disease. Emerging GCGR/GLP-1R dual agonists such as survodutide and mazdutide demonstrate superior efficacy in weight reduction and metabolic disease management compared to selective GLP-1R agonists alone 4, 5, with mazdutide recently approved for obesity and type 2 diabetes treatment 5.