Cytokeratins comprise a diverse group of intermediate filament proteins (IFPs) that are expressed as pairs in both keratinized and non-keratinized epithelial tissue. Cytokeratins play a critical role in differentiation and tissue specialization and function to maintain the overall structural integrity of epithelial cells. Cytokeratins have been found to be useful markers of tissue differentiation which is directly applicable to the characterization of malignant tumors. For example, Cytokeratins 10 and 13 are expressed highly in a subset of squamous cell carcinomas while Cytokeratin 18 is expressed in a majority of adenocarcinomas and basal cell carcinomas. Cytokeratin 18 contains two major phosphorylation sites on Ser 33 and Ser 52. Phosphorylation of Ser 18 is essential for the association of Cytokeratin 18 with 14-3-3 proteins and is involved in keratin organization and distribution.