Transforming growth factor-β (TGF-β) signaling involves multiple pathways beyond the well-known Smad pathway, including MAP kinase (MAPK), Rho-like GTPase, and phosphatidylinositol-3-kinase (PI3K)/AKT pathways. These non-Smad pathways are activated by TGF-β receptors and play crucial roles in regulating various cellular functions, such as epithelial-mesenchymal transition (EMT), cell migration, and apoptosis. The review discusses recent advances in understanding the molecular mechanisms of these non-Smad pathways and their functions in TGF-β signaling. The Erk MAPK pathway is activated by TGF-β through receptor tyrosine kinase (RTK) signaling, involving the recruitment of Grb2/Sos and subsequent activation of Ras, Raf, and Erk. Erk activation is essential for EMT, which is a key process in TGF-β signaling. The JNK/p38 MAPK pathway is also activated by TGF-β through the TAK1 signaling cascade, which is independent of Smad signaling. This pathway contributes to TGF-β-induced apoptosis and EMT. Rho-like GTPases, such as RhoA, play a role in TGF-β-induced EMT by regulating cytoskeletal dynamics and tight junction dissolution. The PI3K/Akt pathway is involved in TGF-β signaling, contributing to EMT through mTOR/S6K signaling. However, the PI3K/Akt pathway can also antagonize Smad-mediated effects, such as apoptosis and growth inhibition. The review highlights the complexity of TGF-β signaling, where non-Smad pathways interact with Smad pathways to regulate diverse cellular responses. Future research aims to further elucidate the molecular mechanisms of these pathways and their roles in disease. The study emphasizes the importance of understanding these pathways for developing therapeutic strategies targeting TGF-β signaling in various diseases.Transforming growth factor-β (TGF-β) signaling involves multiple pathways beyond the well-known Smad pathway, including MAP kinase (MAPK), Rho-like GTPase, and phosphatidylinositol-3-kinase (PI3K)/AKT pathways. These non-Smad pathways are activated by TGF-β receptors and play crucial roles in regulating various cellular functions, such as epithelial-mesenchymal transition (EMT), cell migration, and apoptosis. The review discusses recent advances in understanding the molecular mechanisms of these non-Smad pathways and their functions in TGF-β signaling. The Erk MAPK pathway is activated by TGF-β through receptor tyrosine kinase (RTK) signaling, involving the recruitment of Grb2/Sos and subsequent activation of Ras, Raf, and Erk. Erk activation is essential for EMT, which is a key process in TGF-β signaling. The JNK/p38 MAPK pathway is also activated by TGF-β through the TAK1 signaling cascade, which is independent of Smad signaling. This pathway contributes to TGF-β-induced apoptosis and EMT. Rho-like GTPases, such as RhoA, play a role in TGF-β-induced EMT by regulating cytoskeletal dynamics and tight junction dissolution. The PI3K/Akt pathway is involved in TGF-β signaling, contributing to EMT through mTOR/S6K signaling. However, the PI3K/Akt pathway can also antagonize Smad-mediated effects, such as apoptosis and growth inhibition. The review highlights the complexity of TGF-β signaling, where non-Smad pathways interact with Smad pathways to regulate diverse cellular responses. Future research aims to further elucidate the molecular mechanisms of these pathways and their roles in disease. The study emphasizes the importance of understanding these pathways for developing therapeutic strategies targeting TGF-β signaling in various diseases.