Involucrin is a precursor protein of the keratinocyte cornified envelope, which is formed beneath the inner surface of the cell membrane during terminal differentiation. Involucrin first appears in the cell cytosol but ultimately becomes cross-linked to membrane proteins by transglutaminase. During keratinocyte terminal differentiation glutamine residues of involucrin become covalently cross-linked to other envelope precursors via covalent ε-(γ-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. Involucrin is specifically expressed in Chinese hamster ovarian cells (fibroblasts), PtK2 rat kangaroo kidney cells (simple epithelial) and rat epidermal keratinocytes (stratifying squamous epithelial).