NUF2 is a core component of the NDC80 kinetochore complex essential for chromosome 1 and spindle checkpoint activity 1. It organizes stable microtubule binding sites at the outer kinetochore and synergistically enhances microtubule affinity with the SKA1 complex 23. Beyond its canonical mitotic role, NUF2 exhibits unexpected functions in ribosome biogenesis by regulating pre-rRNA transcription and maintaining RNA polymerase I components 4. NUF2 is aberrantly overexpressed across multiple human malignancies including cholangiocarcinoma, anaplastic thyroid cancer, gastric cancer, hepatocellular carcinoma, breast cancer, ovarian cancer, and lung adenocarcinoma, where elevated expression correlates with poor prognosis 5678910. NUF2 promotes oncogenic pathways through distinct mechanisms: inhibiting TFR1 autophagic degradation via p38/MAPK signaling in cholangiocarcinoma 5, maintaining magnesium homeostasis to activate mTOR-mediated protein synthesis in thyroid cancer 6, regulating MAPK-dependent G2/M phase transition in gastric cancer 7, and activating Wnt/β-catenin signaling in breast cancer 9. USP7-mediated deubiquitination stabilizes NUF2 to promote SLC7A11-dependent ferroptosis resistance in ovarian cancer 10. NUF2 inhibition induces cell cycle arrest and apoptosis across cancer models, suggesting therapeutic potential as a cancer treatment target 87.