SDR9C7 encodes short-chain dehydrogenase/reductase family 9C member 7. It is crucial for skin barrier function, as it catalyzes the dehydrogenation of lipoxygenase products esterified in acylceramide, which is essential for the covalent attachment of acylceramide to proteins on the outer surface of the cornified cell envelope, a key step in forming the corneocyte lipid envelope (CLE) of the skin's stratum corneum [1,2]. Mutations in this gene are associated with autosomal recessive congenital ichthyosis, highlighting its importance in maintaining skin integrity [3,4].

In a Sdr9c7-KO mouse model, there was a loss of covalent binding of epidermal ceramides to protein, a structural fault in the skin barrier. Quantitative liquid chromatography-mass spectometry (LC-MS) assays in Sdr9c7 -/- epidermis showed almost complete loss of a specific species of ω-O-acylceramide esterified with linoleate-9,10-trans-epoxy-11E-13-ketone, while other acylceramides related to the lipoxygenase pathway were in higher abundance. Recombinant SDR9C7 catalyzed NAD⁺-dependent dehydrogenation, but ichthyosis mutants were inactive [2].

In conclusion, SDR9C7 is essential for skin barrier formation through its role in the covalent binding of acylceramide to proteins. The Sdr9c7-KO mouse model has provided key insights into the molecular mechanisms underlying skin barrier function and the pathogenesis of ichthyosis, emphasizing the importance of this gene in maintaining healthy skin [1,2,4].