Involucrin

Involucrin is a protein encoded by the IVL gene in humans. It is a major component of the cornified cell envelope, the insoluble protective layer that strengthens the outer epidermis and other stratified squamous epithelia. Involucrin is synthesized by differentiating keratinocytes, particularly in the stratum spinosum and stratum granulosum, and is incorporated into the envelope during the final stages of keratinocyte maturation.

As a substrate for transglutaminase 1, involucrin is cross-linked to other envelope proteins such as loricrin and small proline-rich proteins to form a rigid, cross-linked scaffold. The resulting cornified envelope provides barrier function and mechanical resilience to the epidermis. The protein contains repeat-rich regions rich in glutamine and lysine residues that mediate transglutaminase-catalyzed cross-linking and envelope assembly.

Involucrin expression is induced during keratinocyte differentiation and is commonly used as a histological marker of this process. Its expression is regulated by calcium signaling and various differentiation-inducing stimuli, and it is found in other stratified squamous epithelia besides the skin.

Genetic variation in IVL has been associated with epidermal barrier dysfunction and susceptibility to atopic dermatitis in multiple populations, reflecting its role in envelope formation. Abnormal involucrin expression or function can contribute to altered skin barrier properties observed in inflammatory skin diseases.