The faulty R406W/R405W mutant desmin assembly process and its impact on the structure and function of the extrasarcomeric cytoskeleton thus provides an explanation for numerous subsequent pathological lesions in desminopathies comprising i) formation of protein aggregates, ii) defects in the proper alignment and anchorage of the myofibrillar apparatus with concomitant mechanical strain‐induced degenerative alterations and iii) defects in the distribution, morphology and function of mitochondria. Here, DES is linked to Desminopathy.