Pilop et al. demonstrated enriched calpain-mediated proteolysis resulting in increased C-terminal filamin fragments in both MFS and bicuspid aortic valve aortopathy as well as increased vinculin, calponin, and microfibril-associated glycoprotein-4 (MFAP4), further highlighting modulation of SMC function and ECM components as a central process in MFS pathophysiology49. Here, VCL is linked to Marfan syndrome.