ERK 1/2- MAPK signaling defects, TGFbeta-dependent activation of profibrotic processes, defects in cytoskeleton dynamics involving the actin-depolymerizing protein cofilin-1, defects in the desmin network and mitochondrial dysfunction have been found in LmnaH222P/H222P myocardium, and elevated TGFbeta2 levels have been measured in mouse serum, providing a complex picture of LMNA-related cardiomyopathy pathomechanism that links altered signaling regulation to fibrosis and defects in cytoskeleton dynamics, leading to mitochondrial defects and oxidative stress [87,145,147,151,152]. The gene discussed is DES; the disease is cardiomyopathy.