Herein, as part of our ongoing attempts to clarify the biological roles of the PLA2 family using comprehensive gene targeting strategies, we have identified PNPLA1, which represents an ichthyosis-causative gene with unknown function29, as an enzyme essential for the biosynthesis of acylceramide, a unique lipid component, the presence of which has long been recognized as prerequisite for normal skin barrier function. The gene discussed is PNPLA1; the disease is ichthyosis.