Labeling for the proliferation marker Ki-67 was increased in the affected subjects’ skin (Figure S4). This indicates that suprabasal keratinocytes are subject to an abnormal terminal-differentiation program, which provides a possible explanation for thickening of the epidermis and impairment of the epidermal barrier in our affected individuals with mutant GRHL2, although it is unclear why the most prominent skin scaling was found around the margins of the soles. We also noted reduced expression of TERT in the affected individuals’ skin and keratinocytes. Overexpression of GRHL2 in normal keratinocytes increases telomerase activity and increases replicative life span (TERT and PCNA [MIM 176740]). In contrast, knockdown of GRHL2 represses the expression of these genes.12