TGFB1 and Marfan syndrome: These syndromes have been considered as TGF-β signalopathies, as the causal mutations are either direct components of the TGF-β signaling pathway or, as in the case of MFS, a component of the microfibrils in the ECM, FBN1, that is known to bind latent TGF-β in complex with latent TGF-β binding proteins (LTBPs) (Cannaerts et al., 2015; Ramirez et al., 2004; Robertson et al., 2015).