KRTDAP (keratinocyte differentiation-associated protein) functions as a marker of squamous epithelial differentiation and keratinocyte development. The protein is involved in regulating keratinocyte differentiation pathways and may act as a soluble regulator in embryonic skin morphogenesis 1. In normal tissue biology, KRTDAP expression is elevated in keratocystic odontogenic tumors and other squamous epithelial tissues, indicating its role in promoting differentiated keratinocyte phenotypes 1. Clinically, KRTDAP has emerged as a cancer-associated biomarker across multiple malignancies. It is specifically upregulated in HPV-negative head and neck squamous cell carcinoma (HNSCC) and serves as a diagnostic biomarker distinguishing HPV-negative from HPV-positive cases 2. Similarly, KRTDAP is upregulated in oral squamous cell carcinoma (OSCC) and associated with well-differentiated tumors 3. In melanoma, KRTDAP functions as both a diagnostic and prognostic biomarker 4. Conversely, decreased KRTDAP expression characterizes cancer stem-like cells in primary oral squamous cell carcinomas, correlating with reduced cell adhesion capacity 5. KRTDAP dysregulation via abnormal methylation also associates with osteosarcoma metastasis-free survival 6. These findings suggest KRTDAP's dual role: promoting differentiation in normal and some differentiated tumors while being suppressed in undifferentiated, stem-like cancer populations.