KRT78 (keratin 78) is a structural protein belonging to the intermediate filament family that plays a critical role in epithelial differentiation and tissue organization. As a component of keratin filaments, KRT78 is essential for maintaining the structural integrity of the epidermis and corneal epithelium 1. The gene is epigenetically regulated by TET2-mediated 5-hydroxymethylation in terminally differentiated corneal epithelial cells 1, where it is co-expressed alongside other differentiation markers like MUC16 and keratin 12. KRT78 expression is significantly downregulated in head and neck squamous cell carcinoma (HNSCC) compared to normal tissues 23, where reduced expression correlates with poor overall survival, higher tumor grade, and advanced clinical stage 3. Similarly, KRT78 shows low expression in oropharyngeal carcinoma and metastatic melanoma 45. Conversely, KRT78 serves as a component of diagnostic biomarker panels in other conditions: it contributes to COPD classification and comorbidity differentiation 6, and appears as a novel fusion partner in pediatric B-cell acute lymphoblastic leukemia 7. Additionally, KRT78 expression in plasma-derived exosomes is reduced in silicosis patients and inversely correlates with TNF-α levels 8. These findings position KRT78 as a potential diagnostic and prognostic biomarker across multiple diseases, with particular utility in cancer and occupational disease assessment.