If activated properly, TGF-β signaling has an essential role in normal physiology ranging from embryonic development to adult tissue homeostasis, whereas sustained activation or functional deletion via genetic mutations or environmental stimuli will exacerbate its adversary effects, and contribute to the pathophysiology of major diseases such as musculoskeletal disorders, cancer progression and organs fibrosis. The gene discussed is TGFB1; the disease is musculoskeletal system disorder.