Ceramide Synthase 4 Controls Epidermal Lipid Composition and Barrier Function

The study identified Ceramide synthase 4 (CerS4) as a crucial regulator of epidermal barrier maintenance, but not its formation, by inactivating CerS4 in mouse epidermis. The loss of CerS4 disrupted epidermal lipid homeostasis, leading to increased levels of key epidermal surface lipids, such as cholesterol and -hydroxylated ultra-long chain ceramides, and elevated filaggrin expression and processing. This imbalance resulted in skin conditions like acanthosis and hyperkeratosis. The research highlighted a switch from CerS3 to CerS4 and -5 in adult epidermis, suggesting that CerS4 plays a central role in maintaining the skin barrier, offering new insights into lipid-associated skin disorders.