CENPO (centromere protein O) is a constitutive centromeric protein functioning as a component of the CENPA-CAD complex, which recruits kinetochore proteins and regulates chromosome 2 and mitotic progression. At the molecular level, CENPO modulates kinetochore-bound NDC80 complex levels and may facilitate CENPA incorporation into centromeres through CENPA-NAC interactions. In cancer biology, CENPO emerges as a pan-cancer oncogene with significant clinical relevance. CENPO is upregulated in most cancers including lung adenocarcinoma, gastric cancer, hepatocellular carcinoma, and bladder cancer 123. High CENPO expression correlates with poor prognosis, advanced TNM stage, and reduced overall and disease-free survival 12. Conversely, in prostate cancer, low CENPO expression associates with shorter cancer-specific survival 4. Functionally, CENPO knockdown in cancer models suppresses cell proliferation, migration, invasion, and induces apoptosis 123. Mechanistically, CENPO regulates growth through ATM signaling in gastric cancer and mTOR/CDK1/6 pathways in lung adenocarcinoma 23. CENPO expression correlates with immune infiltration, particularly myeloid-derived suppressor cells, and associates with immune checkpoint inhibitor response 13. These findings identify CENPO as a potential pan-cancer prognostic biomarker and therapeutic target with immunotherapeutic implications.