DES and cardiomyopathy: Depletion of Nesprin-3 or its binding partner desmin leads to a nucleus collapse, loss of genome organization, DNA damage and broad transcriptional changes that may contribute to the pathophysiological changes observed in desmin-related cardiomyopathies (Heffler et al., 2020), highlighting an important role of the desmin cytoskeleton in nuclear stability and genome organization.