TGFB3 encodes transforming growth factor beta-3, a multifunctional signaling protein that plays critical roles in development, tissue homeostasis, and pathological processes. The protein is produced as a latent complex that requires activation through integrin-independent mechanisms, with TGFβ3 having a lower activation threshold compared to TGFβ1 1. Unlike TGFβ1, TGFβ3 expression is significantly increased in human fibrotic tissues and independently contributes to fibrosis pathogenesis in mouse models 1. The protein functions through dynamic allosteric mechanisms, where binding events can expose the active domain without complete dissociation from its latent complex 2. TGFB3 promotes scarless healing in fetal wounds and reduced scarring in adults, contrasting with TGFβ1's pro-fibrotic effects 3. In cardiac tissue, TGFB3 expression is regulated by Hippo-Yap signaling and contributes to sinoatrial node homeostasis 4. Pathogenic variants in TGFB3 cause Loeys-Dietz syndrome type 5, characterized by heritable thoracic aortic disease, though with later onset and lower penetrance compared to TGFBR1/2-related forms 56. Genetic polymorphisms in TGFB3 have been associated with congenital hearing impairment 7.