SNTB2 is a PDZ domain-containing scaffold protein that functions as a molecular adaptor for organizing membrane protein localization and linking receptors to the cytoskeleton and dystrophin-associated glycoprotein complex 1. It binds to GPCRs such as the α1D-adrenergic receptor through C-terminal PDZ ligand interactions, regulating plasma membrane localization and signaling 1. SNTB2 also interacts with adiponectin receptor 1, potentially regulating receptor protein levels 2. In metabolic regulation, SNTB2 influences adipocyte lipid droplet expansion and lipid homeostasis. SNTB2-deficient mice show reduced adiposity and diminished adipocyte hypertrophy on high-fat diet, with enhanced fatty acid clearance and reduced systemic glucose 3. However, SNTB2 and alpha-syntrophin appear to exert opposite effects on lipid droplet regulation 3. SNTB2 influences sphingomyelin metabolism and ERK signaling but not ABCA1-mediated HDL cholesterol regulation 4. Clinically, SNTB2 has emerging relevance in cancer. Its expression increases in radioresistant lung cancer cells, with SNTB2 knockdown enhancing radiosensitivity 5. SNTB2 was identified as a macrophage-related immunomarker in metastatic melanoma, where high SNTB2 expression correlates with poor prognosis and reduced CD8+ T cell infiltration 6. These findings suggest SNTB2 may contribute to both metabolic diseases and cancer progression.