Filagriini

Filagriini, or filaggrin in English, is a structural protein of the epidermis encoded by the FLG gene in humans. It plays a key role in the formation and maintenance of the skin barrier and in maintaining skin hydration. Filaggrin is synthesized as profilaggrin, a large precursor stored in keratohyalin granules within keratinocytes of the stratum granulosum. Proteolytic processing releases filaggrin monomers, which bind and compact keratin intermediate filaments, promoting the collapse of keratinocytes into the flattened corneocytes that form the stratum corneum.

As filaggrin is degraded, its breakdown products contribute to the natural moisturizing factor (NMF) of the skin. These components, including various amino acids and organic acids such as urocanic and pyroglutamic/pyrrolidone carboxylic acids, help retain moisture, maintain skin pH, and support barrier function. The gene’s expression is highest in terminally differentiating epidermal cells, particularly in the outermost layers of the epidermis.

Genetic variants in FLG that reduce or abolish filaggrin production are among the strongest risk factors for impaired barrier function. Loss-of-function mutations are strongly associated with ichthyosis vulgaris and are a major predisposing factor for atopic dermatitis and related allergic outcomes, often accompanied by increased transepidermal water loss and dry skin. Regulation of filaggrin expression is influenced by keratinocyte differentiation signals and inflammatory cues, with certain cytokines linked to decreased expression in inflammatory skin conditions.