CENPE (centromere protein E) is a microtubule plus-end-directed kinetochore motor protein essential for proper chromosome 4 during mitosis. The protein plays critical roles in chromosome 4, microtubule-kinetochore attachment, and spindle assembly checkpoint activation to prevent aneuploidy 1. CENPE functions by mediating lateral sliding of chr4 along spindle microtubules toward the spindle equator and maintaining stable kinetochore-microtubule connections. Mechanistically, CENPE acts as a processive bi-directional tracker of dynamic microtubule tips and requires its interaction with other checkpoint proteins like BUB1B for proper spindle assembly checkpoint function. Disease relevance is significant, as heterozygous mutations in CENPE cause primary microcephaly 13 23, characterized by reduced brain size due to impaired neural stem cell proliferation and increased apoptosis. Additionally, CENPE is upregulated in multiple cancers including medulloblastoma 4, acute myeloid leukemia 5, and cervical cancer 6, where it promotes tumor progression through cell cycle regulation and p53 pathway modulation. Clinically, CENPE serves as both a prognostic biomarker for various cancers and a potential therapeutic target, with inhibitors having entered clinical trials for cancer treatment 1.