ArticleThe Journal of investigative dermatology2017
PNPLA1 Deficiency in Mice and Humans Leads to a Defect in the Synthesis of Omega-O-Acylceramides.
Article in The Journal of investigative dermatology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Alterations of Ultra Long-Chain Fatty Acids in Hereditary Skin Diseases-Review Article.Frontiers in medicine · 2021Pooled it
- Discovery of Dihydroxy-Ketone-Type Protein-Bound Ceramides as the Dominant Type in Human Stratum Corneum.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Biallelic GLTP mutations cause nonsyndromic epidermal differentiation disorder via disrupted epidermal glucosylceramide transport.The Journal of clinical investigation · 2026Article
- A standardized approach to test missenseJID innovations : skin science from molecules to population health · 2026Article
- Dysregulated cholesterol metabolism in genodermatoses: implications for systemic disease and therapeutic strategies.Frontiers in cell and developmental biology · 2026Review
- Specific organelle targeting as a key step in epidermal lipid synthesis.Frontiers in medicine · 2026Article
- Prevalence and genotypic distribution of non-epidermolytic ichthyosis in Italian Golden Retrievers.PloS one · 2026Article
- Defective targeting of PNPLA1 to lipid droplets causes ichthyosis in ABHD5-syndromic epidermal differentiation disorder.Journal of lipid research · 2025Article
- Human genetic defects of sphingolipid synthesis.Journal of inherited metabolic disease · 2025Review
- Determining the structure of protein-bound ceramides, essential lipids for skin barrier function.iScience · 2023Article
- The PNPLA family of enzymes: characterisation and biological role.Arhiv za higijenu rada i toksikologiju · 2023Article
- Role of Omega-Hydroxy Ceramides in Epidermis: Biosynthesis, Barrier Integrity and Analyzing Method.International journal of molecular sciences · 2023Review
- Sphingosine 1-Phosphate as Essential Signaling Molecule in Inflammatory Skin Diseases.International journal of molecular sciences · 2023Review
- Identification andMedicina (Kaunas, Lithuania) · 2023Article
- Advances in the treatment of autosomal recessive congenital ichthyosis, a look towards the repositioning of drugs.Frontiers in pharmacology · 2023Review
- Treatments for Non-Syndromic Inherited Ichthyosis, Including Emergent Pathogenesis-Related Therapy.American journal of clinical dermatology · 2022Review
- Review
- KLF5 governs sphingolipid metabolism and barrier function of the skin.Genes & development · 2022Article
- Inheritance of Monogenic Hereditary Skin Disease and Related Canine Breeds.Veterinary sciences · 2022Review
- PNPLA1-Mediated Acylceramide Biosynthesis and Autosomal Recessive Congenital Ichthyosis.Metabolites · 2022Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Mutations in PNPLA1 have been identified as causative for autosomal recessive congenital ichthyosis in humans and dogs. So far, the underlying molecular mechanisms are unknown. In this study, we generated and characterized PNPLA1-deficient mice and found that PNPLA1 is crucial for epidermal sphingolipid synthesis. The absence of functional PNPLA1 in mice impaired the formation of omega-O-acylceramides and led to an accumulation of nonesterified omega-hydroxy-ceramides. As a consequence, PNPLA1-deficient mice lacked a functional corneocyte-bound lipid envelope leading to a severe skin barrier defect and premature death of newborn animals. Functional analyses of differentiated keratinocytes from a patient with mutated PNPLA1 demonstrated an identical defect in omega-O-acylceramide synthesis in human cells, indicating that PNPLA1 function is conserved among mammals and indispensable for normal skin physiology. Notably, topical application of epidermal lipids from wild-type onto Pnpla1-mutant mice promoted rebuilding of the corneocyte-bound lipid envelope, indicating that supplementation of ichthyotic skin with omega-O-acylceramides might be a therapeutic approach for the treatment of skin symptoms in individuals affected by omega-O-acylceramide deficiency.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.