ZFP750 affects the cutaneous barrier through regulating lipid metabolism

an essential function of the epidermis is to provide a physical barrier that prevents the loss of water. essential mediators of this barrier function include ceramides, cholesterol, and very long chain fatty acids, and their al-teration causes human pathologies, including psoriasis and atopic dermatitis. a frameshift mutation in the human ZNF750 gene, which encodes a zinc finger transcription factor, has been shown to cause a seborrhea-like dermatitis. Here, we show that genetic deletion of the mouse homolog ZFP750 results in loss of epidermal barrier function, which is associated with a substantial reduction of ceramides, nonpolar lipids. the alteration of epidermal lipid homeostasis is directly linked to the transcriptional activity of ZFP750. ZFP750 directly and/or indirectly regulates the expression of crucial enzymes primarily involved in the biosynthesis of ceramides. overall, our study identifies the transcription factor ZFP750 as a master regulator epidermal homeostasis through lipid biosynthesis and thus contributing to our understanding of the pathogenesis of several human skin diseases.