GPBAR1 (G protein-coupled bile acid receptor 1, also known as TGR5) is a G protein-coupled receptor that functions as a bile acid sensor on cell membranes 12. Bile acid binding triggers conformational changes that activate Gs protein-coupled signaling, leading to adenylate cyclase activation and increased cAMP production 12. GPBAR1 responds to multiple bile acids including lithocholate, deoxycholate, and cholate 2. Beyond lipid digestion, GPBAR1 mediates bile acids' roles as signaling molecules regulating energy expenditure, tissue inflammation, and glucose metabolism 34. In metabolic tissues, GPBAR1 activation promotes energy expenditure and reduces adiposity in brown adipose tissue, while regulating GLP-1 secretion in enteroendocrine cells 4. GPBAR1 dysregulation contributes to multiple diseases: underactivation during dysbiosis impairs energy expenditure and promotes lipogenesis in nonalcoholic fatty liver disease 5, while aberrant activation on cancer-associated fibroblasts promotes cholangiocarcinoma progression through CXCL10-mediated immunosuppression 6. Additionally, GPBAR1 signaling in cardiomyocytes protects against diabetic cardiomyopathy by suppressing cardiac fatty acid uptake 7. These diverse functions establish GPBAR1 as a critical metabolic integrator with significant therapeutic potential across metabolic and neoplastic diseases.