TGFBR2 is a transmembrane serine/threonine kinase receptor that binds transforming growth factor beta ligands (TGFB1, TGFB2, TGFB3) with picomolar affinity and mediates TGF-β signaling through SMAD2/3 phosphorylation 1. The receptor regulates diverse cellular processes including epithelial-mesenchymal transition, stem cell differentiation, and immune cell function. Mechanistically, TGFBR2 heterodimerizes with TGFBR1 upon ligand binding to activate downstream SMAD signaling and modulate reactive oxygen species metabolism 1. The receptor undergoes endocytosis and autophagy-mediated degradation, processes regulated by PIEZO1-dependent mechanisms 2. Clinical significance is substantial: heterozygous TGFBR2 mutations cause Loeys-Dietz syndrome type I, characterized by aggressive aortic aneurysms, arterial tortuosity, hypertelorism, and craniofacial abnormalities, with mean age at death of 22.6 years 3. Despite loss-of-function mutations, affected tissues paradoxically show increased TGF-β signaling 4, suggesting dominant-negative effects. TGFBR2 mutations also associate with Marfan syndrome-related aneurysm development 5. Therapeutically, TGFBR2 knockout or inhibition in CAR T and NK cells enhances anti-tumor immunity against solid tumors, glioblastoma, and hepatocellular carcinoma by preventing TGF-β-mediated immune suppression 678.