<scp>C</scp>dk5 regulates multiple cellular events in neural development, function and disease

<jats:p>Cyclin‐dependent kinases (<jats:styled-content style="fixed-case">CDK</jats:styled-content>s) generally regulate cell proliferation in dividing cells, including neural progenitors. In contrast, an unconventional <jats:styled-content style="fixed-case">CDK</jats:styled-content>,<jats:styled-content style="fixed-case"> C</jats:styled-content>dk5, is predominantly activated in post‐mitotic cells, and involved in various cellular events, such as microtubule and actin cytoskeletal organization, cell–cell and cell–extracellular matrix adhesions, and membrane trafficking. Interestingly, recent studies have indicated that <jats:styled-content style="fixed-case">C</jats:styled-content>dk5 is associated with several cell cycle‐related proteins, Cyclin‐<jats:styled-content style="fixed-case">E</jats:styled-content> and p27<jats:sup>kip1</jats:sup>. Taking advantage of multiple functionality, <jats:styled-content style="fixed-case">C</jats:styled-content>dk5 plays important roles in neuronal migration, layer formation, axon elongation and dendrite arborization in many regions of the developing brain, including cerebral cortex and cerebellum. <jats:styled-content style="fixed-case">C</jats:styled-content>dk5 is also required for neurogenesis at least in the cerebral cortex. Furthermore, <jats:styled-content style="fixed-case">C</jats:styled-content>dk5 is reported to control neurotransmitter release at presynaptic sites, endocytosis of the <jats:styled-content style="fixed-case">NMDA</jats:styled-content> receptor at postsynaptic sites and dendritic spine remodeling, and thereby regulate synaptic plasticity and memory formation and extinction. In addition to these physiological roles in brain development and function, <jats:styled-content style="fixed-case">C</jats:styled-content>dk5 is associated with many neurodegenerative diseases, such as <jats:styled-content style="fixed-case">A</jats:styled-content>lzheimer's disease, <jats:styled-content style="fixed-case">P</jats:styled-content>arkinson's disease and amyotrophic lateral sclerosis. In this review, I will introduce the physiological and pathological roles of <jats:styled-content style="fixed-case">C</jats:styled-content>dk5 in mammalian brains from the viewpoint of not only <jats:italic>in vivo</jats:italic> phenotypes but also its molecular and cellular functions.</jats:p>