Microtubules are involved in several cellular processes, including chromosome segregation, cell division and cell motility. Many of these functions are regulated by microtubule-associated proteins. Here, Chen and colleagues identify a new microtubule-associated protein with a role in cytokinesis. Through a large-scale protein localization analysis of human open reading frames (ORFs), the authors observed that the protein encoded by one ORF, KIAA1383, showed strong association with microtubules; they renamed it MTR120 (microtubule regulator 120 KDa). The localization of MTR120 to microtubules depended on a region in its middle domain that is rich in positively charged residues, a feature of microtubule-binding domains in other proteins. MTR120 promoted microtubule stabilization in vitro, and its loss in cells led to defects in cytokinesis as well as polyploidy.