To ensure proper attachment of all chromosomes to the spindle, PLK1 has to associate with kinetochores during prometaphase and must be released from these sites before sister chromatid separation can begin. The monoubiquitylation of PLK1 by the ubiquitin ligase CUL3-KLHL22 is now identified as a critical step in promoting the release of PLK1 from kinetochores, pushing non-proteolytic ubiquitylation into the limelight of cell division research.