Targeting the palm: a leap forward toward treatment of keratin disorders

Any rational therapy benefits from an understanding of basic biology and the simplicity of its strategy. Among keratinopathies, epidermolytic palmoplantar keratoderma stands out by virtue of hotspot mutations in the KRT9 gene, exclusively expressed in the palmoplantar epidermis. In this issue, Leslie Pedrioli et al. report on the successful application of KRT9-specific siRNAs in cultured cells and in a mouse model. The study beautifully illustrates the potency of a thorough experimental approach and the challenges that remain, especially in its delivery.