Cytokeratins

Cytokeratins are a subfamily of intermediate filament proteins expressed by epithelial cells. They belong to a large gene family that encodes more than 20 keratins, divided into type I (acidic) and type II (basic to neutral) members. Cytokeratins form obligate heterodimers consisting of one type I and one type II keratin, which then assemble into 10-nanometer intermediate filaments that strengthen the cytoskeleton. The expression of specific keratin pairs is tissue- and differentiation-dependent, producing distinct keratin patterns in different epithelia.

Each cytokeratin protein has a central coiled-coil rod domain flanked by non-keratin head and tail domains. The head and tail regions mediate interactions with other cytoskeletal components and cell junctions, influencing filament organization and cell architecture. In stratified epithelia, basal cells commonly express keratins such as KRT5 and KRT14, while in many simple epithelia keratins such as KRT8 and KRT18 predominate, with additional keratins contributing to regional identity (for example, KRT20 in select tissues).

Functionally, cytokeratins provide mechanical support and distribute mechanical stress within epithelial cells. They also participate in signaling pathways, regulate cell polarity, and contribute to processes such as differentiation and wound healing. In diagnostic pathology, cytokeratins are widely used as immunohistochemical markers to characterize tumors. Keratin expression patterns—such as CK7/CK20, CK5/6, CK14, and CK8/18 profiles—aid in determining tissue of origin, differentiation status, and differentiation from non-epithelial tumors.