TGFBRAP1 (transforming growth factor beta receptor associated protein 1) functions as a multifaceted regulator in both TGF-β signaling and endosomal trafficking pathways. In TGF-β signaling, TGFBRAP1 acts as a positive regulator by interacting with and stabilizing TGF-β receptor type 1 (TGFBR1), competing with E3 ubiquitin ligases Smurf1/2 to prevent receptor degradation 1. This stabilization creates a positive feedback loop, as TGF-β signaling upregulates TGFBRAP1 expression, particularly in drug-resistant cancer stem cells 1. TGFBRAP1 also modulates TGF-β/SMAD7 signaling through interactions with FOXO3, contributing to pulmonary fibrosis pathogenesis 2. In endosomal trafficking, TGFBRAP1 functions as a component of the CORVET complex, mediating early endosome fusion and Rab5-to-Rab7 conversion 3. Overexpression of TGFBRAP1 can disrupt HOPS complex assembly, impairing autophagosome-lysosome fusion and affecting lysosomal hydrolase delivery 3. Clinically, TGFBRAP1 expression correlates with cancer stemness and drug resistance in hepatocellular carcinoma 1, and genetic variants are associated with blood pressure regulation and type 2 diabetes mellitus susceptibility 45.