Smad1 is essential for bone growth, and its deficiency disrupts calvarial bone formation,228 osteoblast-specific deletion causes osteopenia and blunts BMP responses.228 Triple-knockout of Smads1/5/8 causes severe chondrodysplasia, underscoring the functional redundancy among these R-Smads.229 A rare missense mutation in Smad9 (c.65T>C, p. Leu22Pro) causes elevated bone mass,230 establishing Smad9 as a novel high bone mass gene and potential osteoanabolic target. The gene discussed is SMAD9; the disease is Osteopenia.