TGF‐β signalling proceeds through both canonical (Smad‐dependent) and non‐canonical, extracellular signal‐regulated kinase (ERK), c‐Jun N‐terminal kinase (JNK) and p38 mitogen‐activated protein kinase (p38 MAPK)‐dependent pathways.13, 14 Holm et al15 illustrated that selective ERK1/2 blockade reduces aneurysm development in a murine MFS model, whereas compound MFS Fbn1C1039G/+ mutants with Smad4 knockout demonstrated worsened aneurysm severity, suggesting that these divergent TGF‐β pathways may have opposing effects. The gene discussed is SMAD4; the disease is aneurysm.