GLP1R encodes a Family B G-protein coupled receptor that mediates the physiological effects of glucagon-like peptide-1 (GLP-1) 1. Upon ligand binding, GLP1R activates adenylyl cyclase and increases intracellular cAMP levels 1, triggering multiple metabolic responses. In pancreatic beta cells, GLP1R activation potentiates glucose-induced insulin secretion, increases insulin expression, inhibits beta-cell apoptosis, and promotes beta-cell neogenesis 1. GLP1R also reduces glucagon secretion, delays gastric emptying, promotes satiety, and increases peripheral glucose disposal 1. Beyond the pancreas, GLP1R is localized to smooth muscle cells in arterial walls of the kidney and lung, myocytes of the sinoatrial node in the heart, and neurons in the gastrointestinal tract 2. These diverse localizations underlie GLP1R's cardiovascular effects, including blood pressure and heart rate modulation 2. Therapeutically, GLP1R agonists (liraglutide, semaglutide) treat type 2 diabetes and obesity 1. However, important species-specific differences exist: rodent C-cells express high GLP1R levels and respond to agonists with calcitonin release and hyperplasia, while primate thyroid C-cells show minimal GLP1R expression and no proliferative response 3. Notably, some neuroendocrine neoplasms expressing GLP1R show increased proliferation with GLP1R agonist treatment 4, warranting clinical surveillance. Genetic variants in GLP1R influence treatment response to semaglutide, with sex-dependent effects on weight loss 5.