An increased (less acidic) pH can activate proteases with neutral-to-alkaline pH optima to process inactive forms of IL-1α, IL-1β, and IL-18 that are stored in the cytosol of corneocytes.16,38-41 Consistent with this view, Hosomi et al42 showed increased activity of caspase-1 in the SC of patients with Netherton syndrome, an autosomal recessive inherited disease characterized by features of AD and uninhibited breakdown of filaggrin in the SC. The gene discussed is IL1A; the disease is Netherton syndrome.