CENPK (centromere protein K) is a centromeric protein with dual roles in normal cell division and aberrant cancer progression. In normal function, CENPK is a component of the CENPA-CAD complex recruited to centromeres, where it coordinates with KNL1 to facilitate kinetochore assembly and chromosome 5 during mitosis. In cancer contexts, CENPK exhibits oncogenic functions across multiple tumor types. CENPK is significantly overexpressed in cervical cancer, thyroid carcinoma, lung adenocarcinoma, gastric cancer, breast carcinoma, and prostate cancer 1 2 3 4. Elevated CENPK expression associates with poor prognosis and predicts worse overall survival in multiple malignancies 1 5. CENPK promotes cancer cell viability, migration, invasion, and epithelial-mesenchymal transition while conferring chemoresistance 3 6. Mechanistically, CENPK drives tumorigenesis through multiple pathways: it activates Wnt/β-catenin signaling while suppressing p53 in cervical cancer 1, engages PTEN-PI3K-AKT signaling in gastric cancer 7, and activates FAK/PI3K/AKT/mTOR pathways in breast carcinoma 6. Additionally, CENPK splice variants influence drug resistance in prostate cancer 8. CENPK knockdown substantially inhibits tumor growth in vivo and enhances chemotherapeutic sensitivity, positioning CENPK as a promising therapeutic target and prognostic biomarker 1.