Highly insoluble, histidine rich protein that co-purified with keratin intermediate filament protein in epidermal extracts (Dale BA).

Condenses and aligns keratin intermediate filaments.

Filaggrin (FLG) gene comprises three exons.

Mutations are among the most common single gene defects in causation and modification of disease.

Encodes an epidermal protein abundantly expressed in the outer layers of the epidermis.

Approximately 10% of Europeans are heterogeneous carriers of a loss of function mutation in FLG resulting in a 50% reduction in expressed protein.

Gene mutations underlie dermatologic and allergic diseases.

The spectrum of diseases with monogenic disorders of keratinization occurs via abnormalities in epidermal transport of lipids and allergens.

FLG mutation carriers have increased risk for atopic dermatitis, contact allergy, asthma, hay fever, and peanut allergy, and influences the severity of asthma and alopecia areata and susceptibility to herpes infection.

FLG located in epidermal differentiation complex, a cluster of approximately 60 genes in epithelial differentiation on chromosome 1q21.

FLG encodes seven fused S100 proteins:filaggrin, filaggrin-2, honerin, trichohyalin, trichhyalin-like1, cornulin, and repetin.

The epidermal differentiation complex contains other genes, including S100 proteins, loricin, involucrin, small proline-rich proteins, and late cornerfied envelope proteins.

Late cornified envelope proteins implicated with increased susceptibility to psoriasis.

Proflaggrin is expressed late in epidermal differentiation in the granular cell layers of stratified, cornified epithelial cells.

Epidermal granular cell cytoplasm contains dense staining keratohyalin granules, the main constituent is proflaggrin.

Contributes to the formation of the stratum corneum.

Keratohyalin granules act as a reservoir of an inactive proflaggrin, and important protein for squamous formation and maturation.

Filaggrin end proucts are found within cytoplasm of squamous cells of the stratum corneum.

Profilaggrin processing is initiated in transitional cells of the stratum corneum.

Proflaggrin is histidine and glutamine rich, and act as a reservoir of amino acids, modulates the pH of the stratum corneum, retains moisture, and possibly exerts antimicrobial activity.

Deficiency of filaggrin leads to failure in skin barrier.

Ichthyosis vulgaris is the most prevalent disorder of keratinization associated with loss of function mutations in FLG.

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