One remarkable molecule: filaggrin

Brown, Sara J.; Irwin McLean, W.H.

doi:10.1038/jid.2011.393

Cited by 527Dermatology and Skin DiseasesSkin and Cellular Biology ResearchGenetic and rare skin diseases.

One remarkable molecule: filaggrin

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Brown, Sara J., Irwin McLean, W.H.·2012·Journal of Investigative Dermatology

DOI 10.1038/jid.2011.393PMC PMC3378480

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Abstract

The discovery, in 2006, that loss-of-function mutations in the filaggrin (FLG) gene are the cause of ichthyosis vulgaris-the most common disorder of keratinization-and also a strong genetic risk factor for atopic eczema, marked a significant breakthrough in the understanding of eczema pathogenesis. Subsequent investigations of the role of FLG-null mutations have identified a series of significant associations with atopic disease phenotypes, including atopic asthma, allergic rhinitis, and peanut allergy. However, many questions remain to be answered in relation to the precise mechanisms by which deficiency of an intracellular protein expressed primarily in the differentiating epidermis may contribute to the development of cutaneous and systemic pathology. This review aims to highlight the key milestones in filaggrin research over the past 25 years, to discuss the mechanistic, clinical, and therapeutic implications, and to consider possible future directions for ongoing investigation.

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FLG deficiency and increased TEWL are associated with skin barrier dysfunction and increased allergen sensitization.
“It is also well known that FLG deficiency and increased TEWL are associated with skin barrier dysfunction and increased allergen sensitization (20, 35, 63–65).”
From Particulate matter causes skin barrier dysfunction. (2021) · cites this paper as [35]
The section on maintenance of the skin barrier reports barrier impairment and enhanced allergen sensitization in murine models of filaggrin deficiency. The section on filaggrin deficiency in eczema says transepidermal water loss measures barrier impairment and correlates somewhat with FLG null genotype. It does not establish a separate association between increased TEWL and allergen sensitization. (LLM, conf=0.82)
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Altered penetration of polyethylene glycols into uninvolved skin of atopic dermatitis patients
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Novel filaggrin mutation but no other loss-of-function variants found in Ethiopian patients with atopic dermatitis
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Filaggrin null mutations increase the risk and persistence of hand eczema in subjects with atopic dermatitis: results from a general population study
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Is the Filaggrin–Histidine–Urocanic Acid Pathway Essential for Stratum Corneum Acidification?
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Missing C‐terminal filaggrin expression, NFkappaB activation and hyperproliferation identify the dog as a putative model to study epidermal dysfunction in atopic dermatitis
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Filaggrin Mutations Are Genetic Modifying Factors Exacerbating X-Linked Ichthyosis
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Mapping of the associated phenotype of an absent granular layer in ichthyosis vulgaris to the epidermal differentiation complex on chromosome 1*
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Analysis of four prevalent filaggrin mutations (R501X, 2282del4, R2447X and S3247X) in Austrian and German patients with atopic dermatitis
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Caspase-14 protects against epidermal UVB photo-damage and water loss.
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Nickel reactivity and filaggrin null mutations - evaluation of the filaggrin bypass theory in a general population
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Full Sequencing of the FLG Gene in Italian Patients with Atopic Eczema: Evidence of New Mutations, but Lack of an Association
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Combined occurrence of filaggrin mutations and IL-10 or IL-13 polymorphisms predisposes to atopic dermatitis
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Keratinocytes Cultured From Subjects With Ichthyosis Vulgaris Are Phenotypically Abnormal
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Filaggrin Null Alleles Are Not Associated with Psoriasis
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Analysis of Taiwanese ichthyosis vulgaris families further demonstrates differences inFLGmutations between European and Asian populations
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Diagnostic and prognostic value of antibodies against chimeric fibrin/filaggrin citrullinated synthetic peptides in rheumatoid arthritis
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De Novo Occurrence of the Filaggrin Mutation p.R501X with Prevalent Mutation c.3321delA in a Japanese Family with Ichthyosis Vulgaris Complicated by Atopic Dermatitis
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Elder siblings enhance the effect of filaggrin mutations on childhood eczema: Results from the 2 birth cohort studies LISAplus and GINIplus
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Bleomycin Hydrolase Is Regulated Biphasically in a Differentiation- and Cytokine-dependent Manner
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Ichthyosiform Dermatoses
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Japanese-Specific Filaggrin Gene Mutations in Japanese Patients Suffering from Atopic Eczema and Asthma
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Filaggrin null mutations and association with contact allergy and allergic contact dermatitis: results from a tertiary dermatology clinic
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Efficacy of Combined Peroxisome Proliferator-Activated Receptor-α Ligand and Glucocorticoid Therapy in a Murine Model of Atopic Dermatitis
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Barrier Function in Transgenic Mice Overexpressing K16, Involucrin, and Filaggrin in the Suprabasal Epidermis
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Association of Filaggrin loss‐of‐function‐mutations with atopic dermatitis and asthma in the Early Treatment of the Atopic Child (ETAC) population
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Are filaggrin mutations associated with hand eczema or contact allergy? – we do not know
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Filaggrin Mutation c.3321delA in a Korean Patient with Ichthyosis Vulgaris and Atopic Dermatitis
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Filaggrin loss-of-function variants are associated with atopic comorbidity in pediatric inflammatory bowel disease
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Association between filaggrin null mutations and concomitant atopic dermatitis and contact allergy
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Increased pachyonychia congenita severity in patients with concurrent keratin and filaggrin mutations
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Filaggrin Null Mutations Are Not a Protective Factor for Acne Vulgaris
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Filaggrin mutations are associated with ichthyosis vulgaris in the Bangladeshi population
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Of flaky tails and itchy skin
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Latex allergy and filaggrin null mutations
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Are epidermal defects the key initiating factors in the development of atopic dermatitis?
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Hoste E Kemperman P Devos M Caspase-14 Is Required for Filaggrin Degradation to Natural Moisturizing Factors in the Skin J Invest Dermatol 2011 21654840

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Background
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Authors: Brown, S. J., & Irwin McLean, W. H.
Affiliations: University of Dundee (GB)
ORCID: Brown, Sara J.
Venue: Journal of Investigative Dermatology
Publisher: Elsevier BV
Published: 2012-03
Volume: 132
Issue: 3
Pages: 751-762
ISSN: 0022-202X (ISSN-L)
DOI: 10.1038/jid.2011.393
PMC: PMC3378480
OpenAlex: W2032896969
Cited by: 527
References: 144
Citations by year: 2026: 26 · 2025: 19 · 2024: 25 · 2023: 32 · 2022: 32 · 2021: 49 · 2020: 39 · 2019: 40 · 2018: 33 · 2017: 47 · 2016: 41 · 2015: 36 · 2014: 54 · 2013: 33 · 2012: 21
FWCI: 5.71
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1371 d)
Locations: Journal of Investigative Dermatology (publishedVersion)
PubMed (publishedVersion)
Discovery Research Portal (University of Dundee) (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Wellcome Trust (086398, 092530, 090066/B/09/Z, 086398/Z/08/Z, 092530/Z/10/Z, 090066)
Topics: Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
Keywords: filaggrin, FLG gene, ichthyosis vulgaris, atopic dermatitis, keratinization, allergic asthma, allergic rhinitis, peanut allergy, epidermis, loss-of-function mutations, eczema pathogenesis, filaggrin deficiency
MeSH terms: Filaggrin Proteins, Dermatitis, Atopic, Humans, Intermediate Filament Proteins, Risk Factors, Ichthyosis Vulgaris, Genetic Predisposition to Disease

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