However, studies have documented impairment in the ubiquitin proteasome pathways by mutant αB-crystallin (R120G) (Chen et al., 2005; Zhang et al., 2010, 2019; Gupta et al., 2014) and desmin mutants (Liu et al., 2006a, b) that are linked to cardiomyopathy in humans; suggesting that worsening protein aggregate pathology is linked at least in part to progressive impairment in this arm of the protein quality control machinery. Here, DES is linked to cardiomyopathy.