The first function described for CYLD was the inhibition of the nuclear factor (NF)-κB pathway [1], and mutations that inactivate the carboxyl-terminal deubiquitinating domain of CYLD deregulate the NF-κB activity, leading to the development of skin appendages tumors in patients of familial cylindromatosis [2]. The gene discussed is NFKB1; the disease is familial cylindromatosis.