Although it is likely that activation of the SMAD2 pathway is associated with skeletal defects in various disorders, such as Marfan syndrome [33,34], osteogenesis imperfecta [35], and neurofibromatosis type-1 [36], the molecular mechanisms that explain how an enhanced SMAD2 pathway affects skeletal defects in those disorders remain unclear. The gene discussed is SMAD2; the disease is neurofibromatosis type 1.