Hyperactivation of KLKs (mainly KLK5 and KLK7) in epidermis has been implicated in pathological over-desquamation, a symptom common to a number of skin diseases, including atopic dermatitis and Netherton syndrome (NS) a rare syndrome of severe ichthyosis caused by mutations in Spink5 gene that encodes LEKTI, a multidomain inhibitor of KLKs and other serine proteases [62]. Here, SPINK5 is linked to Netherton syndrome.