CENPU (centromere protein U) is a kinetochore component essential for chromosome 4 during mitosis 1. As a structural component of the CENPA-NAC complex, CENPU facilitates kinetochore assembly and PLK1 localization to mitotic kinetochores, playing critical roles in mitotic progression and chromosome 4. Beyond canonical mitotic functions, CENPU demonstrates oncogenic properties across multiple cancer types. In glioblastoma, CENPU mediates temozolomide resistance by cooperating with TRIM5α to ubiquitinate and degrade RPS3, activating the ERK1/2 pathway and upregulating RAD51 to enhance DNA damage repair 2. In triple-negative breast cancer, CENPU promotes tumorigenesis and stem cell properties by suppressing lysosomal degradation of furin, which processes nerve growth factor to promote cancer stemness 1. In lung adenocarcinoma, CENPU drives proliferation, migration, and invasion through the DNAJC10 effector pathway 3. In hepatocellular carcinoma, CENPU forms a positive feedback loop with E2F6 and E2F1 to promote cell cycle progression 4, while also activating Notch signaling 5. Additional mechanisms involve FOXM1/Wnt/β-catenin pathway activation in cervical cancer 6 and Wnt/β-catenin signaling in non-small cell lung cancer 7. Elevated CENPU expression correlates with poor prognosis across multiple cancer types, suggesting its utility as a therapeutic target 8.