TGFB1 and osteoporosis: SKI negatively regulates Smad-dependent TGF-β signaling by impeding Smad2 and Smad3 activation, preventing nuclear translocation of the SMAD4 complex and inhibiting TGF-β target gene output by competing with p300/CBP for SMAD binding and recruiting transcriptional repressor proteins, such as mSin3A and HDACs.410–412 The neurocutaneous syndrome, neurofibromatosis type 1 (NF1), has skeletal features including kyphoscoliosis, osteoporosis, and tibial pseudoarthrosis.