The higher frequency of mutations detected in KRT10 compared to the other KI genes is mostly due to the spontaneous occurrence of C-to-T transitions affecting the CG dinucleotide in the “hotspot” codon 156, which was mutated in seven patients (n. 8, 9, 12, 14–17), four of whom were sporadic EI cases (n. 8, 9, 12, 16) and two were presenting with mosaic EN (n. 15, 17). Here, PSME3 is linked to epidermolytic ichthyosis.