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Function of Filaggrin and Caspase-14 in Formation and Maintenance of the Epithelial Barrier
Richard B. Presland
Dermatol Sinica 27: 1-14, 2009

Stratifi ed epithelia line all external and internal body surfaces of mammals and function to
protect us from water loss, environmental insults, chemical damage, and infection. This protective
barrier is composed of a complex mixture of structural proteins and specialized lipids that
together form the anuclear squames of the stratum corneum. Filaggrin and caspase-14 are two
genes expressed in the granular layer of epidermis and other stratified keratinizing epithelia.
Filaggrin is a keratin-binding protein present in the lower layers of the stratum corneum which
plays a key role in barrier function. Filaggrin is synthesized as a large precursor, profi laggrin,
that undergoes specific processing during keratinocyte differentiation to produce filaggrin. In
the middle and upper layers of the stratum corneum, fi laggrin is degraded to free amino acids
which have several functions including water adsorption. Recent work has shown that loss-offunction
mutations in the fi laggrin (FLG) gene cause the dry skin disease ichthyosis vulgaris.
Similar FLG variants are strongly associated with the common infl ammatory skin disease atopic
dermatitis (eczema). Current studies suggest that~50% of European patients with moderate to
severe eczema carry one or more FLG null alleles. Caspase-14 is a member of the caspase family
of aspartate-specifi c proteases that is co-expressed with fi laggrin within the epidermis. Recent
work has shown that it functions both as a profi laggrin protease and protects against UV irradiation.
These studies emphasize the importance of proteases in regulating profi laggrin/fi laggrin and
caspase-14 function, and their common and overlapping roles in epithelial barrier homeostasis.

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