CALCA and keratoconus: In addition, Reactome pathway enrichment analysis [34] identified Keratinization pathway commonly enriched for both transition KC and differentiated KC, whereas Metabolism, Formation of Cornified Envelope, Metabolism of Lipids, and Biological Oxidations pathways were uniquely enriched in terminally differentiated KC (Fig. 5f), consistent with drastically increased lipid and cornified envelope production in these barrier layers.