Smad transcription factors are central to the TGFβ signaling pathway, which is one of the most versatile cytokine signaling pathways in metazoan biology. Recent advances have improved understanding of Smad activation, deactivation, nucleocytoplasmic dynamics, and the assembly of transcriptional complexes. Smad proteins regulate gene expression in response to TGFβ signals, and their function is controlled by a variety of regulatory mechanisms. The TGFβ family includes several members, such as TGFβ, nodals, activins, BMPs, myostatin, and AMH, which have diverse roles in cell division, differentiation, migration, adhesion, and death. The TGFβ signaling pathway is complex, and Smad proteins are key components that mediate the signaling process. Smad proteins are divided into several classes, with RSmads (Smad1, 2, 3, 5, 8) acting as substrates for TGFβ receptors, and Smad4 serving as a common partner for all RSmads. Smad6 and Smad7 are inhibitory Smads that interfere with Smad-receptor or Smad-Smad interactions. Smad proteins have two conserved domains, the MH1 and MH2 domains, which are involved in DNA binding and protein-protein interactions. The MH1 domain is a DNA-binding module stabilized by a zinc atom, while the MH2 domain is a protein-interacting module that mediates interactions with other proteins. Smad activation and deactivation are regulated by phosphorylation and dephosphorylation events, which control their nucleocytoplasmic shuttling and their ability to form transcriptional complexes. Smad proteins undergo a constant process of nucleocytoplasmic shuttling, and their nuclear accumulation results from receptor-mediated phosphorylation events. Smad proteins can interact with various DNA-binding cofactors to regulate gene expression. The Smad pathway is involved in a wide range of biological processes, including cell proliferation, differentiation, and tissue development. The regulation of Smad signaling is complex, and the interaction of Smad proteins with other transcription factors is crucial for the pleiotropic nature of TGFβ signaling. The study of Smad signaling has provided important insights into the mechanisms of gene regulation and the integration of signaling pathways in cells.Smad transcription factors are central to the TGFβ signaling pathway, which is one of the most versatile cytokine signaling pathways in metazoan biology. Recent advances have improved understanding of Smad activation, deactivation, nucleocytoplasmic dynamics, and the assembly of transcriptional complexes. Smad proteins regulate gene expression in response to TGFβ signals, and their function is controlled by a variety of regulatory mechanisms. The TGFβ family includes several members, such as TGFβ, nodals, activins, BMPs, myostatin, and AMH, which have diverse roles in cell division, differentiation, migration, adhesion, and death. The TGFβ signaling pathway is complex, and Smad proteins are key components that mediate the signaling process. Smad proteins are divided into several classes, with RSmads (Smad1, 2, 3, 5, 8) acting as substrates for TGFβ receptors, and Smad4 serving as a common partner for all RSmads. Smad6 and Smad7 are inhibitory Smads that interfere with Smad-receptor or Smad-Smad interactions. Smad proteins have two conserved domains, the MH1 and MH2 domains, which are involved in DNA binding and protein-protein interactions. The MH1 domain is a DNA-binding module stabilized by a zinc atom, while the MH2 domain is a protein-interacting module that mediates interactions with other proteins. Smad activation and deactivation are regulated by phosphorylation and dephosphorylation events, which control their nucleocytoplasmic shuttling and their ability to form transcriptional complexes. Smad proteins undergo a constant process of nucleocytoplasmic shuttling, and their nuclear accumulation results from receptor-mediated phosphorylation events. Smad proteins can interact with various DNA-binding cofactors to regulate gene expression. The Smad pathway is involved in a wide range of biological processes, including cell proliferation, differentiation, and tissue development. The regulation of Smad signaling is complex, and the interaction of Smad proteins with other transcription factors is crucial for the pleiotropic nature of TGFβ signaling. The study of Smad signaling has provided important insights into the mechanisms of gene regulation and the integration of signaling pathways in cells.