ArticleProceedings of the National Academy of Sciences of the United States of America2015
Essential role of the cytochrome P450 CYP4F22 in the production of acylceramide, the key lipid for skin permeability barrier formation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 167 citations in OpenAlex.
- Alterations of Ultra Long-Chain Fatty Acids in Hereditary Skin Diseases-Review Article.Frontiers in medicine · 2021Pooled it
- CYP4F22-Related Autosomal Recessive Congenital Ichthyosis Associated With Hirschsprung Disease and Bartter-Like Renal Manifestations.Journal of medical cases · 2026Article
- Identification of Pathogenic Variants inInternational journal of molecular sciences · 2026Article
- A standardized approach to test missenseJID innovations : skin science from molecules to population health · 2026Article
- Specific organelle targeting as a key step in epidermal lipid synthesis.Frontiers in medicine · 2026Article
- Structural basis of VLCFA chain-length determination by the KCS6-CER2 complex in plants.Science advances · 2025Article
- Comprehensive lipid analysis of human meibum and tears.Scientific reports · 2025Article
- The curious family of cytochrome P450 4F fatty acid ω-hydroxylases: recent developments in their function and relevance for human health.Open biology · 2025Review
- Nonsense Variant in CYP4F22 Causes Malformation of Corneocyte Lipid Envelopes in a Lamellar Ichthyosis Patient.Acta dermato-venereologica · 2025Article
- Metabolic pathways of eicosanoids-derivatives of arachidonic acid and their significance in skin.Cellular & molecular biology letters · 2025Review
- Disorders of fatty acid homeostasis.Journal of inherited metabolic disease · 2025Review
- Human genetic defects of sphingolipid synthesis.Journal of inherited metabolic disease · 2025Review
- Roles of Individual Human Cytochrome P450 Enzymes in Drug Metabolism.Pharmacological reviews · 2024Review
- The fatty acid omega hydroxylase genes (CYP4 family) in the progression of metabolic dysfunction-associated steatotic liver disease (MASLD): An RNA sequence database analysis and review.Biochemical pharmacology · 2024Review
- Skin Lipid Barrier: Structure, Function and Metabolism.Allergy, asthma & immunology research · 2024Review
- Analysis of Active Components and Transcriptome ofInternational journal of molecular sciences · 2024Article
- The role of the cytochrome P450 superfamily in the skin.Expert reviews in molecular medicine · 2024Review
- Body Weight Correlates with Molecular Variances in Patients with Cancer.Cancer research · 2024Article
- Tricarboxylic acid (TCA) cycle, sphingolipid, and phosphatidylcholine metabolism are dysregulated inHeliyon · 2023Article
- Role of Omega-Hydroxy Ceramides in Epidermis: Biosynthesis, Barrier Integrity and Analyzing Method.International journal of molecular sciences · 2023Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A skin permeability barrier is essential for terrestrial animals, and its impairment causes several cutaneous disorders such as ichthyosis and atopic dermatitis. Although acylceramide is an important lipid for the skin permeability barrier, details of its production have yet to be determined, leaving the molecular mechanism of skin permeability barrier formation unclear. Here we identified the cytochrome P450 gene CYP4F22 (cytochrome P450, family 4, subfamily F, polypeptide 22) as the long-sought fatty acid ω-hydroxylase gene required for acylceramide production. CYP4F22 has been identified as one of the autosomal recessive congenital ichthyosis-causative genes. Ichthyosis-mutant proteins exhibited reduced enzyme activity, indicating correlation between activity and pathology. Furthermore, lipid analysis of a patient with ichthyosis showed a drastic decrease in acylceramide production. We determined that CYP4F22 was a type I membrane protein that locates in the endoplasmic reticulum (ER), suggesting that the ω-hydroxylation occurs on the cytoplasmic side of the ER. The preferred substrate of the CYP4F22 was fatty acids with a carbon chain length of 28 or more (≥C28). In conclusion, our findings demonstrate that CYP4F22 is an ultra-long-chain fatty acid ω-hydroxylase responsible for acylceramide production and provide important insights into the molecular mechanisms of skin permeability barrier formation. Furthermore, based on the results obtained here, we proposed a detailed reaction series for acylceramide production.
Indexed as
Identifiers
What OpenQuestion holds
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.