filaggrine

Filaggrin is a filament-aggregating protein essential for epidermal barrier formation in vertebrates. In humans it is encoded by the FLG gene, located on chromosome 1q21 within the epidermal differentiation complex.

Filaggrin is produced as profilaggrin, a large precursor stored in keratohyalin granules of the stratum granulosum. During differentiation profilaggrin is proteolytically processed to multiple filaggrin monomers, which bind to and help aggregate keratin intermediate filaments, promoting the collapse of keratinocytes into flattened corneocytes and contributing to the formation of the cornified envelope.

In the later stages of cornification, filaggrin is degraded to free amino acids and other breakdown products such as urocanic acid and pyrrolidone carboxylic acid, which act as natural moisturizing factors that help maintain skin hydration and acidity.

Genetic mutations in FLG that reduce or abolish filaggrin expression are common risk factors for ichthyosis vulgaris and atopic dermatitis, with barrier dysfunction leading to increased transepidermal water loss and greater permeability to allergens and microbes. The effect is variable and influenced by environment and other genes.

Filaggrin expression is upregulated during keratinocyte differentiation and is mainly produced in the granular layer of the epidermis. Its proper function supports the structural integrity of the stratum corneum and contributes to the skin’s protective properties.