Filaggrin

Filaggrin is a filament-associated protein that binds to keratin fibers in epithelial cells. It is encoded by the FLG gene. Filaggrin is crucial for skin barrier function and water retention. Mutations in the FLG gene are associated with skin conditions such as Ichthyosis vulgaris and Atopic dermatitis.

Structure

Filaggrin is a large protein that is synthesized as a polyprotein precursor, profilaggrin, in the granular layer of the epidermis. Profilaggrin is a large, heavily phosphorylated protein that comprises multiple filaggrin units and a small, basic, amino-terminal peptide. During the terminal differentiation of the epidermis, profilaggrin is dephosphorylated and proteolytically processed into individual filaggrin molecules.

Function

Filaggrin plays a key role in epidermal homeostasis by regulating the barrier function and hydration of the skin. It aggregates keratin filaments, aiding in the collapse of the granular cells into the squames (flat, dead cells) that constitute the stratum corneum, the outermost layer of the epidermis. Filaggrin also contributes to skin hydration by its breakdown into natural moisturizing factors (NMFs), including amino acids, pyrrolidone carboxylic acid, and urocanic acid.

Clinical significance

Mutations in the FLG gene are associated with several skin conditions. The most common of these is Ichthyosis vulgaris, a genetic skin disorder characterized by dry, scaly skin. Filaggrin mutations are also strongly associated with Atopic dermatitis, a chronic, itchy skin condition. In addition, filaggrin mutations have been linked to other allergic diseases, including Asthma and Allergic rhinitis.

See also

• Keratin
• Epidermis (skin)
• Ichthyosis vulgaris
• Atopic dermatitis

References

Filaggrin Resources
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