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TGF-β superfamily signaling pathways emerged with the evolution of multicellular animals, suggesting that these pathways contribute to the increased diversity and complexity required for the development and homeostasis of these organisms. In this review we begin by exploring some key developmental and disease processes requiring TGF-β ligands to underscore the fundamental importance of these pathways before delving into the molecular mechanism of signal transduction, focusing on recent findings. Finally, we discuss how these ligands act as morphogens, how their activity and signaling range is regulated, and how they interact with other signaling pathways to achieve their specific and varied functional roles.