Loss-of-function mutations or deficiency of SMAD2, SMAD3, and SMAD4 genes in mice or humans lead to the formation of aortic aneurysms or dissections, suggesting that basal TGF-βsignaling canonical signaling is indispensable for maintaining the integrity of aortic structure and function. The gene discussed is SMAD2; the disease is aortic aneurysm.