Mitotic interactions of the Nek9 kinase. This figure illustrates what is currently known about the potential upstream regulation and downstream targets of the Nek9 kinase during mitosis. It also suggests possible mechanisms by which Nek9 might regulate spindle organization, although these currently remain only hypotheses. Cdk1 can phosphorylate Nek9 in vitro and both proteins localize to the centrosome; hence, it is possible that Nek9 is activated upon mitotic entry by Cdk1/cyclin B. Once active, it is attractive to speculate that Nek9 may regulate chromatin-mediated microtubule nucleation as Nek9 can interact with Ran through its RCC1-like and catalytic domains. However, it is yet to be shown whether Nek9 influences Ran activity or vice versa. Equally, Nek9 may regulate centrosome-mediated microtubule nucleation and/or anchoring via its interactions with the γ-tubulin ring complex (γ-TuRC) and BicD2, respectively. Finally, Nek9 is proposed to activate two other NIMA-related kinases, Nek6 and Nek7, and, although substrates of Nek6 and Nek7 remain to be identified, it is likely that these also play important roles in mitotic spindle organisation and chromosome segregation.