NUF2 is a structural component of the NDC80 kinetochore complex essential for chromosome 1 and spindle checkpoint control. It organizes stable microtubule binding sites at the outer kinetochore and synergistically enhances microtubule affinity through interaction with the SKA1 complex. Beyond its canonical mitotic role, NUF2 has emerged as a critical regulator of ribosome biogenesis, where it promotes pre-rRNA transcription and maintains nucleolar function during interphase 1. NUF2 is significantly upregulated 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 2345678. In cholangiocarcinoma, NUF2 drives progression via the p38/MAPK pathway by inhibiting autophagic degradation of TFR1 2. In anaplastic thyroid cancer, it maintains intracellular magnesium homeostasis to enhance protein synthesis through PI3K/Akt/mTOR signaling 3. In gastric cancer, NUF2 promotes G2/M phase transition and apoptosis inhibition; the natural product quercetin acts as a selective NUF2 inhibitor with anti-tumor activity 4. In ovarian cancer, the deubiquitinase USP7 stabilizes NUF2 to promote progression through SLC7A11-mediated ferroptosis resistance 7. These findings establish NUF2 as a validated therapeutic target across cancer types.