The transforming growth factor-β (TGFβ) signaling pathway has been extensively studied over the past decade, revealing its complex role in cellular behavior and disease. TGFβ signaling is essential for developmental processes and tissue homeostasis, and its multifunctional nature has been increasingly recognized. However, the question of how the cellular context determines the response to TGFβ remains a key challenge. Recent advances have provided new insights into this mystery, highlighting the importance of context in shaping TGFβ signaling outcomes. TGFβ signaling is mediated through a series of receptors and SMAD proteins, which transmit signals from the cell membrane to the nucleus. The context in which TGFβ is activated determines the specific effects it has on the cell, as different cellular environments can lead to distinct outcomes, such as cell proliferation, differentiation, or apoptosis. This context-dependent response is influenced by various factors, including the availability of TGFβ ligands, the presence of co-receptors, and the epigenetic state of the cell. The TGFβ signaling pathway is regulated by a complex network of interactions, including the SMAD signaling cycle, which involves the phosphorylation and degradation of SMAD proteins. These proteins play a central role in the transcriptional regulation of target genes, and their activity is modulated by various factors, including other signaling pathways such as WNT, MAPK, and PI3K. The integration of these pathways is crucial for the proper functioning of TGFβ signaling in different cellular contexts. In addition to its role in normal development and homeostasis, TGFβ signaling is also involved in pathological processes such as cancer, fibrosis, and immune disorders. In cancer, TGFβ can have dual roles, acting as a tumor suppressor in pre-malignant cells but promoting invasion and metastasis in advanced cancers. This duality highlights the complexity of TGFβ signaling and the need for a deeper understanding of its context-dependent functions. The study of TGFβ signaling has led to significant advances in understanding the molecular mechanisms underlying its diverse biological effects. These findings have important implications for the development of therapeutic strategies targeting TGFβ pathways in diseases such as cancer, fibrosis, and autoimmune disorders. Future research will focus on elucidating the precise mechanisms by which TGFβ signaling is regulated in different cellular contexts and how these mechanisms can be harnessed for therapeutic purposes.The transforming growth factor-β (TGFβ) signaling pathway has been extensively studied over the past decade, revealing its complex role in cellular behavior and disease. TGFβ signaling is essential for developmental processes and tissue homeostasis, and its multifunctional nature has been increasingly recognized. However, the question of how the cellular context determines the response to TGFβ remains a key challenge. Recent advances have provided new insights into this mystery, highlighting the importance of context in shaping TGFβ signaling outcomes. TGFβ signaling is mediated through a series of receptors and SMAD proteins, which transmit signals from the cell membrane to the nucleus. The context in which TGFβ is activated determines the specific effects it has on the cell, as different cellular environments can lead to distinct outcomes, such as cell proliferation, differentiation, or apoptosis. This context-dependent response is influenced by various factors, including the availability of TGFβ ligands, the presence of co-receptors, and the epigenetic state of the cell. The TGFβ signaling pathway is regulated by a complex network of interactions, including the SMAD signaling cycle, which involves the phosphorylation and degradation of SMAD proteins. These proteins play a central role in the transcriptional regulation of target genes, and their activity is modulated by various factors, including other signaling pathways such as WNT, MAPK, and PI3K. The integration of these pathways is crucial for the proper functioning of TGFβ signaling in different cellular contexts. In addition to its role in normal development and homeostasis, TGFβ signaling is also involved in pathological processes such as cancer, fibrosis, and immune disorders. In cancer, TGFβ can have dual roles, acting as a tumor suppressor in pre-malignant cells but promoting invasion and metastasis in advanced cancers. This duality highlights the complexity of TGFβ signaling and the need for a deeper understanding of its context-dependent functions. The study of TGFβ signaling has led to significant advances in understanding the molecular mechanisms underlying its diverse biological effects. These findings have important implications for the development of therapeutic strategies targeting TGFβ pathways in diseases such as cancer, fibrosis, and autoimmune disorders. Future research will focus on elucidating the precise mechanisms by which TGFβ signaling is regulated in different cellular contexts and how these mechanisms can be harnessed for therapeutic purposes.