TGFB1 is a multifunctional cytokine regulating cell growth, differentiation, and immune function across diverse tissues. Functionally, TGFB1 is secreted as an inactive complex bound to latency-associated peptide (LAP) and activation-regulating molecules (LTBP1, LRRC32, LRRC33). Integrins (αVβ6 and αVβ8) release active TGFB1 by distorting the LAP structure, enabling binding to TGF-β receptors (TGFBR1/2) and SMAD2/3 phosphorylation-mediated signaling. TGFB1 exhibits pleiotropic effects: it promotes osteoblastic bone formation, drives intestinal epithelial regeneration through fetal reprogramming via YAP/TEAD and SOX9 activation, and induces epithelial-to-mesenchymal transition (EMT) in mammary epithelial cells through context-dependent SMAD3 signaling 12. TGFB1 also regulates immune responses, promoting either regulatory T cells (high concentrations) or Th17 cells (low concentrations with IL-6/IL-21) [UniProt]. Mechanistically, TGFB1 activates miR-9-dependent G-quadruplex formation and enhancer-promoter chr19 looping during transcriptional activation 3. Clinically, TGFB1 dysregulation associates with osteoarthritis (via enhancer SNP rs75621460), pulmonary arterial hypertension (through BMP/TGF-β pathway disruption), colorectal cancer progression, and prostate cancer risk (overexpression linked to increased PCa development) 4567. Regulatory SNPs in TGFB1 (rs1800469) significantly increase cervical cancer risk 8.