We focused on Cx26, which is expressed at extremely low, oftentimes undetectable levels in epidermal keratinocytes, yet, paradoxically, mutant Cx26 leaky/hyperactive HCs cause genodermatoses, including keratitis-ichthyosis-deafness syndrome (KID) and palmoplantar keratoderma with deafness (PPKDFN) that may drastically compromise quality of life and life-long health [40,51,52] (Table 1). This evidence concerns the gene GJB2 and hereditary palmoplantar keratoderma.