Mutations in TGF-β receptors and SMAD3 (a key component of TGF-β canonical signal pathways) occur in patients with aneurysms associated with Loeys–Dietz syndrome (LDS), MFS, aneurysm-osteoarthritis syndrome (AOS) and familial thoracic aortic aneurysms and dissections (FTAAD)11, 12, 13: these discoveries point to the complexity of the role(s) of TGF-β signaling in the pathogenesis of aneurysms6, 8. Here, SMAD3 is linked to familial thoracic aortic aneurysm and aortic dissection.