BMP6 is a TGF-β superfamily growth factor with dual roles in skeletal development and iron homeostasis. Functionally, BMP6 promotes bone and cartilage formation 1 while serving as a critical regulator of systemic iron metabolism by stimulating hepcidin (HAMP) expression through interaction with hemojuvelin and its receptor BMPR1A/ALK3 23. BMP6 initiates canonical signaling by binding type I receptor ACVR1 and type II receptor ACVR2B, leading to SMAD1/5/8 phosphorylation and nuclear translocation 4. Additionally, BMP6 modulates non-canonical pathways including TAZ-Hippo and VEGF signaling 5. Clinically, BMP6 dysregulation associates with iron overload disorders. The endothelial mTORC2-Foxo1 axis senses iron levels and directly activates BMP6 transcription to regulate hepcidin, with therapeutic potential in hereditary hemochromatosis 6. BMP5 functionally cooperates with BMP6 in hepcidin regulation, particularly when BMP6 is limited 7. In cancer, BMP6 functions as a tumor suppressor through gene methylation-mediated silencing, affecting epithelial-mesenchymal transition and cell proliferation variably across cancer types 8. BMP6 polymorphisms associate with osteonecrosis risk in sickle cell anemia 9, and emerging evidence implicates BMP6 in diabetic cardiorenal complications via endothelial cell communication 10.