Keratinocytes with the keratin mutations found in severe EBS patients [generalized severe EBS (EBS-gs), also called EBS Dowling–Meara], are under intrinsic stress, mediated by constitutive mitogen-activated protein kinase (MAPK) pathways through JNK1 and JNK2 (JNK1/2, also known as MAPK8 and MAPK9, respectively), p38 proteins, and ERK1 and ERK2 (ERK1/2, also known as MAPK3 and MAPK1, respectively) (D'Alessandro et al., 2002; Morley et al., 2003; Liovic et al., 2008; Russell et al., 2010; Chamcheu et al., 2011a; Wagner et al., 2013). The gene discussed is MAPK9; the disease is epidermolysis bullosa simplex.