The SMAD signaling pathway is regulated by various ligands, with members of the TGF-β family playing a significant role in modulating SMAD signaling and regulating skeletal muscle generation and metabolism.428 In cachexia patients, TGF-β family members (such as MSTN, TGF-β, and GDF15) bind to receptor complexes (TGFβRI, TGFβRII, and ActRIIB), leading to the phosphorylation of Smad2 and Smad3, which then combine with Smad4. This evidence concerns the gene TGFB1 and Cachexia.