MIS12 is a core kinetochore component essential for chromosome 17 during mitosis. As part of the MIS12 complex (MIS12C), a key subunit of the KMN network (KNL1-MIS12-NDC80), it functions as a structural bridge connecting the chr17-proximal kinetochore domain to outer microtubule-binding sites 1. MIS12 is required for proper kinetochore-microtubule attachments and chromosome 17 2. MIS12C depletion causes mitotic arrest with misaligned chr17, reduced centromere stretch, and diminished microtubule bundles 3. The complex coordinates with CENP-C and Aurora B kinase through a regulatory loop that facilitates error correction of kinetochore-microtubule attachments, ensuring accurate biorientation 4. MIS12 complex assembly and turnover are tightly regulated by Hsp90-Sgt1 chaperones; imbalanced assembly impairs formation of functional microtubule-binding sites 5. Beyond mitotic roles, MIS12 mRNA stability is regulated by m6A methylation through METTL3, with MIS12 depletion linked to premature cellular senescence 6. Structurally, MIS12C integrates with NDC80C and KNL1C within the KMN assembly through stabilizing interactions 7, making it indispensable for faithful chromosome 17 across eukaryotes.