CENP-E is a large protein of ∼312 kDa consisting of an NH2-terminal kinesin motor domain tethered to a globular COOH-terminal domain via an extended “rod” domain predicted to form a coiled coil. Kinesin motors hydrolyze ATP to produce directed mechanical force along microtubules. In the case of CENP-E, the motor activity is involved in establishing and maintaining stable connections between mitotic chromosomes and the microtubules of the mitotic spindle. CENP-E exhibits a periodic accumulation and loss, with maximal levels found during late G₂ and M-phases of the cell cycle, and minimum levels in early G_1. CENP-E is thus appropriately spatially and temporally positioned to integrate the regulation of the mitotic checkpoint with the mechanics of chromosome-microtubule interactions.