GPBAR1 (also known as TGR5) is a G protein-coupled receptor for bile acids that mediates metabolic and inflammatory signaling. Upon bile acid binding, GPBAR1 undergoes conformational change and couples to Gs proteins to activate adenylate cyclase, initiating downstream signaling cascades. The receptor is activated by multiple bile acid species including lithocholate, deoxycholate, chenodeoxycholate, and cholate. Beyond their classical role in lipid absorption, bile acids function as signaling molecules through GPBAR1 to regulate energy homeostasis, with activation promoting energy expenditure and adiposity reduction in brown adipose tissue 1 and involved in glucose-dependent peptide-1 secretion. GPBAR1 signaling modulates metabolic diseases including obesity, type 2 diabetes, and nonalcoholic fatty liver disease through coordinated control of lipid and carbohydrate metabolism 2. In nonalcoholic fatty liver disease, dysregulation of bile acid metabolism leads to underactivation of GPBAR1, causing decreased energy expenditure and increased lipogenesis 3. In cholangiocarcinoma, GPBAR1 activation on cancer-associated fibroblasts promotes an immunosuppressive tumor microenvironment and metastasis; GPBAR1 inhibition combined with pembrolizumab enhances therapeutic efficacy 4. These findings establish GPBAR1 as a therapeutic target for metabolic and oncologic diseases.