TGFB2 is a multifunctional cytokine that regulates angiogenesis, heart development, and eye development. The protein is synthesized as an inactive precursor; after cleavage in the Golgi apparatus, the latency-associated peptide (LAP) remains non-covalently bound to mature TGF-β2, keeping it sequestered in the extracellular matrix. Interaction between LAP and regulatory molecules such as LTBP1 and LRRC32/GARP maintains latency until activation releases the mature protein, which then signals through TGF-β receptors (TGFBR1 and TGFBR2). Beyond development, TGFB2 operates in diverse pathological contexts: it promotes epithelial-to-mesenchymal transition and metastasis in gastric cancer via the Smad/METTL3 axis 1, confers radioresistance in lung cancer through epigenetic upregulation by KDM4C 2, and drives gemcitabine resistance in pancreatic ductal adenocarcinoma by reprogramming lipid metabolism 3. TGFB2 also contributes to ischemic heart failure pathology through apoptosis promotion 4 and supports microglial survival in the central nervous system 5. Mutations in TGFB2 cause Loeys-Dietz syndrome, an aortic aneurysm disorder characterized paradoxically by increased TGF-β signaling despite loss-of-function mutations 6. Therapeutically, TGFB2 inhibition shows promise; the compound imperatorin combined with gemcitabine demonstrates synergistic effects in resistant pancreatic cancer models 3. Approved agents targeting the TGF-β pathway include fresolimumab, bintrafusp alfa, and luspatercept.