Involucrin is a precursor protein of the keratinocyte cornified envelope, which is formed beneath the inner surface of the cell membrane during terminal differentiation. During keratinocyte terminal differentiation, glutamine residues of involucrin become covalently cross-linked to other envelope precursors via covalent epsilon- (gamma-glutamyl) lysine bonds. Moreover, its large size allows involucrin to cross-link molecules that are separated by substantial distances in the cornified envelope. These properties allow a single involucrin molecule to form multiple cross-links, in multiple spatial planes, with other envelope precursors.