Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGF-β) family, which bind to type I and type II serine-threonine kinase receptors and transduce signals through Smad and non-Smad pathways. BMPs have a wide range of biological activities in various tissues, including bone, cartilage, blood vessels, heart, kidney, neurons, liver, and lung. Recent studies have shown that BMP signaling is finely regulated by various mechanisms, both positive and negative. Disruptions in BMP signaling pathways are linked to a variety of clinical disorders, including vascular diseases, skeletal diseases, and cancer. Recombinant BMP ligands and increased endogenous BMP expression have therapeutic effects on some diseases. The development of BMP receptor inhibitors may also be useful for some clinical diseases caused by hyperactivation of the BMP signaling pathway. BMPs are divided into several subgroups, including BMP-2/4, BMP-5/6/7/8, GDF-5/6/7, and BMP-9/10. Each subgroup has distinct functions and binding specificities. BMP receptors include type I and type II receptors, which are essential for signal transduction. Type I receptors include ALK-1-7, while type II receptors include BMPR-II, ActR-II, and ActR-IIB. Coreceptors such as RGM proteins enhance BMP signaling. BMP signaling is regulated by various mechanisms, including protein modifications like dephosphorylation, ubiquitination, sumoylation, and ectodomain shedding. BMP signaling is transduced through Smad pathways, with R-Smads (Smad1, Smad5, Smad8) and co-Smads (Smad4) playing key roles. I-Smads (Smad6, Smad7) act as antagonists of R-Smad signaling. Smad signaling is also regulated by non-Smad pathways, including the TAK1 pathway, which is involved in cell proliferation and differentiation. Mutations in BMP receptors and Smad genes can lead to various diseases, including vascular abnormalities, skeletal disorders, and cancer. Small-molecule inhibitors for BMP receptors have been developed and show potential for treating clinical disorders. Smad signaling is crucial for transcription of target genes and is regulated by various factors, including phosphatases and ubiquitin-proteasome pathways. Overall, BMP signaling is a complex process involving multiple pathways and mechanisms that are essential for various biological functions.Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGF-β) family, which bind to type I and type II serine-threonine kinase receptors and transduce signals through Smad and non-Smad pathways. BMPs have a wide range of biological activities in various tissues, including bone, cartilage, blood vessels, heart, kidney, neurons, liver, and lung. Recent studies have shown that BMP signaling is finely regulated by various mechanisms, both positive and negative. Disruptions in BMP signaling pathways are linked to a variety of clinical disorders, including vascular diseases, skeletal diseases, and cancer. Recombinant BMP ligands and increased endogenous BMP expression have therapeutic effects on some diseases. The development of BMP receptor inhibitors may also be useful for some clinical diseases caused by hyperactivation of the BMP signaling pathway. BMPs are divided into several subgroups, including BMP-2/4, BMP-5/6/7/8, GDF-5/6/7, and BMP-9/10. Each subgroup has distinct functions and binding specificities. BMP receptors include type I and type II receptors, which are essential for signal transduction. Type I receptors include ALK-1-7, while type II receptors include BMPR-II, ActR-II, and ActR-IIB. Coreceptors such as RGM proteins enhance BMP signaling. BMP signaling is regulated by various mechanisms, including protein modifications like dephosphorylation, ubiquitination, sumoylation, and ectodomain shedding. BMP signaling is transduced through Smad pathways, with R-Smads (Smad1, Smad5, Smad8) and co-Smads (Smad4) playing key roles. I-Smads (Smad6, Smad7) act as antagonists of R-Smad signaling. Smad signaling is also regulated by non-Smad pathways, including the TAK1 pathway, which is involved in cell proliferation and differentiation. Mutations in BMP receptors and Smad genes can lead to various diseases, including vascular abnormalities, skeletal disorders, and cancer. Small-molecule inhibitors for BMP receptors have been developed and show potential for treating clinical disorders. Smad signaling is crucial for transcription of target genes and is regulated by various factors, including phosphatases and ubiquitin-proteasome pathways. Overall, BMP signaling is a complex process involving multiple pathways and mechanisms that are essential for various biological functions.