Polo-like kinases (PLKs) are evolutionarily conserved kinases essential for cell division, proliferation, and development. These kinases are characterized by the presence of a C-terminal phosphor-peptide-interaction domain, the polo-box domain (PBD). Cdc5 (Msd2) is a cell cycle serine/threonine-protein kinase of Saccharomyces cerevisiae involved in mitotic exit. Recently, a novel function for Cdc5 as an important regulator of cellular ploidy has been reported.