The skin is subjected to continuous physical stress. Keratinocytes resist mechanical stress by tethering the tension-bearing keratin intermediate filament cytoskeleton to sites of intercellular contact known as desmosomes (Garrod and Chidgey, 2008; Green and Simpson, 2007). The plakin protein desmoplakin (DP) is an obligate desmosomal constituent necessary for keratin anchorage at cell-cell contacts. Establishing and maintaining the DP-keratin association is essential for regulating desmosomal adhesive strength in both developing epidermis and adult stratified tissue (Huen et al., 2002;