While active TGF-β is required for pathogenesis, the relative contribution of fibronectin, which also binds LAP (44) to fibrillin-1–mediated sequestration of latent TGF-β, is unclear, but our findings challenge the prevailing concept that increased bioavailability of TGF-β is a direct consequence of fibrillin-1 deficiency in MFS. Here, FN1 is linked to Marfan syndrome.