A study in type III patients with OI showed upregulation of TGF‐β signaling, highlighting this protein's central role in the pathogenesis of OI.(11) Types III and IV patients exhibited increased phospho‐SMAD2 staining in bone sections, supporting the preclinical finding of increased TGF‐β activity in OI bone.(12) In fact, regulation of SMAD phosphorylation was the most significantly upregulated molecular event, whereas TGF‐β activation was identified as the most significant upstream regulator. The gene discussed is SMAD2; the disease is osteogenesis imperfecta.