KIF2C (kinesin family member 2C) is a microtubule depolymerase essential for mitotic progression and chromosome 1. In complex with KIF18B, KIF2C constitutes the major microtubule plus-end depolymerizing activity in mitotic cells 1. It regulates microtubule turnover at kinetochores and functions in chromosome 1 2, chromosome 1, and the lateral to end-on conversion of kinetochore-microtubule attachments 3. Mechanistically, KIF2C contains an N-terminal Tudor/PWWP/MBT fold that binds phosphorylated motifs 4, enabling it to form biomolecular condensates that concentrate PLK1 and phosphorylated BRCA2 at microtubule extremities, amplifying catalytic activities during kinetochore attachment 4. Clinically, KIF2C dysregulation drives multiple cancer hallmarks. High KIF2C expression correlates with poor prognosis in breast cancer, lung cancer, and hepatocellular carcinoma 5. KIF2C promotes chemoresistance by preferentially depolymerizing polyglutamylated tubulin, even in the presence of paclitaxel 6. Beyond cell cycle regulation, KIF2C participates in tumor immunosuppression by regulating macrophage M2 polarization through the STAT3/IL-10 axis 7 and activating the JAK2/STAT3 pathway in clear cell renal cell carcinoma 8. These mechanisms establish KIF2C as a promising therapeutic target for combating chemoresistance and enhancing immunotherapy outcomes 9.