There is a marked increase in cytokines, including interferon gamma, in cutaneous diseases such as atopic dermatitis and psoriasis. In this issue of the Journal, Tawada and colleagues demonstrate that the quantity of ultra long-chain ceramides in the stratum corneum, which play a key role in maintaining the permeability barrier, is reduced in atopic dermatitis and psoriasis. Further, they demonstrate that interferon gamma decreases the expression of the enzymes required for the synthesis of these ultra long-chain ceramides (ELOVLs and ceramide synthase 3). These results suggest that an increase in interferon gamma by decreasing the key enzymes required for the synthesis of ultra long-chain ceramides could further impair permeability barrier function, thereby exacerbating the pathological changes.