Twice switched at birth: Cell cycle-independent roles of the “neuron-specific” cyclin-dependent kinase 5 (Cdk5) in non-neuronal cells

Cdk5 (cyclin-dependent kinase 5 or initially NCLK for neuronal CDC2-like kinase) was switched twice at its birth nearly twenty years ago: first it was thought to be cyclin-dependent, second it was assumed to be primarily of importance in neuronal cells—both turned out not to be the case. In this review we want to discuss issues of pharmacological inhibition, to highlight the versatile roles, and to summarize the growing evidence for the functional importance of Cdk5 in non-neuronal tissues, such as blood cells, tumor cells, epithelial cells, the vascular endothelium, testis, adipose and endocrine tissues. The organizing principles we follow are apoptosis/cell death, migration/motility, aspects of inflammation, and, finally, secretion/metabolism.

► Cdk5 has important functions in non-neuron cells.
► Selective pharmacological inhibition of Cdk5 is still debatable.
► Cdk5 plays important roles in blood cells, tumor cells, epithelial and endothelial cells, as well as endocrine tissues and adipocytes.
► Cdk5 might evolve as attractive drug target for various non-neurologic diseases.