TGF-β is a central mediator of fibrogenesis, involved in fibrotic diseases through activation and upregulation, modulating fibroblast phenotype and function, and inducing myofibroblast transdifferentiation. The canonical ALK5/Smad3 pathway is critical in fibrosis, while Smad-independent pathways may regulate Smad activation or directly transduce fibrogenic signals. TGF-β promotes matrix preservation and deposition by enhancing matrix protein synthesis and altering the balance between matrix-preserving and matrix-degrading signals. It also induces the expression of CTGF, which enhances TGF-β activity and contributes to fibrogenic responses. TGF-β signaling pathways include Smad-dependent and Smad-independent pathways, with the Smad3 pathway playing a key role in fibrosis. TGF-β inhibition has been shown to reduce fibrosis in various animal models, highlighting its role in fibrotic conditions. However, TGF-β's pleiotropic effects and role in tissue homeostasis, immunity, and cell proliferation raise concerns about potential side effects of TGF-β blockade. TGF-β signaling is involved in fibroblast phenotype and function, myofibroblast differentiation, and matrix remodeling. TGF-β also plays a role in epithelial-mesenchymal transition (EMT) and endothelial-mesenchymal transition (EndMT), contributing to fibrotic remodeling. TGF-β signaling pathways are critical in the pathogenesis of fibrosis, with Smad3 inhibition showing promise as a therapeutic approach. However, the functional pleiotropy of TGF-β and its role in tissue repair and immune regulation raise concerns about the safety of TGF-β inhibitors.TGF-β is a central mediator of fibrogenesis, involved in fibrotic diseases through activation and upregulation, modulating fibroblast phenotype and function, and inducing myofibroblast transdifferentiation. The canonical ALK5/Smad3 pathway is critical in fibrosis, while Smad-independent pathways may regulate Smad activation or directly transduce fibrogenic signals. TGF-β promotes matrix preservation and deposition by enhancing matrix protein synthesis and altering the balance between matrix-preserving and matrix-degrading signals. It also induces the expression of CTGF, which enhances TGF-β activity and contributes to fibrogenic responses. TGF-β signaling pathways include Smad-dependent and Smad-independent pathways, with the Smad3 pathway playing a key role in fibrosis. TGF-β inhibition has been shown to reduce fibrosis in various animal models, highlighting its role in fibrotic conditions. However, TGF-β's pleiotropic effects and role in tissue homeostasis, immunity, and cell proliferation raise concerns about potential side effects of TGF-β blockade. TGF-β signaling is involved in fibroblast phenotype and function, myofibroblast differentiation, and matrix remodeling. TGF-β also plays a role in epithelial-mesenchymal transition (EMT) and endothelial-mesenchymal transition (EndMT), contributing to fibrotic remodeling. TGF-β signaling pathways are critical in the pathogenesis of fibrosis, with Smad3 inhibition showing promise as a therapeutic approach. However, the functional pleiotropy of TGF-β and its role in tissue repair and immune regulation raise concerns about the safety of TGF-β inhibitors.