Mutations in Recessive Congenital Ichthyoses Illuminate the Origin and Functions of the Corneocyte Lipid Envelope

Debra Crumrine, Denis Khnykin, Peter Krieg, Mao Qiang Man, Anna Celli, Theodora M. Mauro, Joan S. Wakefield, Gopinathan Menon, Elizabeth Mauldin, Jeffrey H. Miner, Meei Hua Lin, Alan R. Brash, Eli Sprecher, Franz P.W. Radner, Keith Choate, Dennis Roop, Yoshikazu Uchida, Robert Gruber, Matthias Schmuth, Peter M. Elias

Research output: Contribution to journalShort surveypeer-review

25 Scopus citations


The corneocyte lipid envelope (CLE), a monolayer of ω-hydroxyceramides whose function(s) remain(s) uncertain, is absent in patients with autosomal recessive congenital ichthyoses with mutations in enzymes that regulate epidermal lipid synthesis. Secreted lipids fail to transform into lamellar membranes in certain autosomal recessive congenital ichthyosis epidermis, suggesting the CLE provides a scaffold for the extracellular lamellae. However, because cornified envelopes are attenuated in these autosomal recessive congenital ichthyoses, the CLE may also provide a scaffold for subjacent cornified envelope formation, evidenced by restoration of cornified envelopes after CLE rescue. We provide multiple lines of evidence that the CLE originates as lamellar body-limiting membranes fuse with the plasma membrane: (i) ABCA12 patients and Abca12 –/– mice display normal CLEs; (ii) CLEs are normal in Netherton syndrome, despite destruction of secreted LB contents; (iii) CLEs are absent in VSP33B-negative patients; (iv) limiting membranes of lamellar bodies are defective in lipid-synthetic autosomal recessive congenital ichthyoses; and (v) lipoxygenases, lipase activity, and LIPN co-localize within putative lamellar bodies.

Original languageEnglish
Pages (from-to)760-768
Number of pages9
JournalJournal of Investigative Dermatology
Issue number4
StatePublished - Apr 2019


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