BMP5 is a secreted growth factor of the TGF-β superfamily with essential roles in skeletal development, iron homeostasis, and placental function. BMP5 initiates canonical BMP signaling by binding type I receptor BMPR1A and type II receptor BMPR2, leading to SMAD1/5/8 phosphorylation and nuclear translocation to regulate target gene transcription 1. The protein can also activate non-canonical pathways including MAPK p38 signaling to promote chondrogenic differentiation 2. Beyond skeletal development, BMP5 plays critical roles in systemic iron homeostasis by regulating hepcidin expression, with loss of Bmp5 alleles causing iron loading and hemochromatosis, particularly when combined with Bmp6 deficiency 3. In placental biology, BMP5 is differentially expressed between adherent and non-adherent sites in placenta accreta spectrum disorder, with reduced N-glycosylated BMP5 levels in preeclamptic placentas; N-glycosylation of BMP5 promotes trophoblast proliferation, migration, invasion, and angiogenesis via BMP5-SMAD1/5 signaling 45. In pancreatic biology, BMP5 is the predominately expressed BMP ligand in beta cells, with elevated BMP5 signaling in type 2 diabetes reducing glucose-stimulated insulin secretion, while BMP5 knockdown enhances beta cell function 6. BMP5 also contributes to mandibular ossification through paracrine signaling mechanisms 7.