Genetic screens led to the discovery of the first PLKs, Cdc5 and Polo, in budding yeast and Drosophila melanogaster, respectively. PLKs are involved at multiple stages during mitosis and meiosis. PLKs are present in all branches of the Eukarya, and that vertebrates have five paralogues: the Ser/Thr protein kinases PLK1–5.  These motifs can be organized in different configurations to regulate PLK activity, localization and function. The ancestral member of the family is PLK1; at least three duplication events gave rise to PLK2–5. All PLKs share similar architecture: they have an amino-terminal (Ser/Thr) catalytic kinase domain and a carboxy-terminal region containing two or more PBs, which are organized in different domains. PLK1–3 have very similar catalytic domains, whereas that of PLK4 has a divergent primary sequence, and PLK5 includes a pseudokinase domain. PLK1 target proteins are usually ‘primed’ through phosphorylation by a Pro-directed kinase, such as cyclin-dependent kinase 1 (CDK1) and MAPKs, for optimal binding to PLK1. 
PLK1 inactivates the G2 DNA damage checkpoint in different ways: it phosphorylates claspin, which targets it for degradation and leads to the inactivation of Ser/Thr protein kinase CHK1 and ATR; it phosphorylates tumour suppressor p53-binding protein 1 (p53BP1), which promotes p53BP1 dissociation from DNA and inactivation of CHK2, rendering it unable to bind to its ligands. PLK1 also participates in DNA damage repair through phosphorylation of DNA repair protein RAD51 homologue 1 (RAD51), which results in p53BP1 accumulation at the sites of damage.  PLK2 and PLK4 control centriole duplication. PLK3 is required for G1/S transition, promotes DNA replication, and might also have a role in mitotic progression. In contrast to PLK1 and PLK4, the other three members PLK2, PLK3 and PLK5 are mostly found in non-proliferative tissues, in which they are involved in cell differentiation and, in the case of PLK2 and PLK5, in neuronal activity. Interestingly, PLK2 regulates mitotic spindle orientation in the mammary gland and is required for its development. PLK3 has also been ascribed various functions, such as in programmed cell death148, in the hypoxia signalling pathway, in oxidative and hyperosmotic stress responses, and in the regulation of Golgi fragmentation during the cell cycle. The importance of PLKs in key cell cycle processes is apparent, as the perturbation of these kinases causes multiple diseases.