The essential role of plectin for formation and homeostasis of HDs became clearly evident when patients suffering from EBS-MD, a disease characterized by severe skin blistering (due to rupture and lysis of basal cell layer keratinocytes) and late onset muscular dystrophy were shown to carry mutations in the plectin gene (Rezniczek et al. 2010; Winter and Wiche 2013). Here, PLEC is linked to Menkes disease.