It was discovered 15 years ago, and it is saliently expressed in post-mitotic central nervous system neurons (CNS).

Cdk5 is a proline-directed serine/threonine kinase, which was first identified as a CDK family member due to its similar structure to CDC2/CDK1 in humans, a protein that plays a crucial role in the regulation of the cell cycle.

Some investigations[6] have reported that the active states of protein kinases structurally differ from each other in order to preserve the geometry of its machinery so that catalytic output works properly.

On the other hand, the large lobe, a C-terminal, is helical shaped, which helps to identify the substrate and includes crucial residues for the phospho-transfer.

In order to perform, Cdk5 needs to be activated by p35 (these 3 amino acids, Asp-259, Asn-266, and Ser-270, are involved in the formation of hydrogen bonds with Cdk5[11]) or p39 (the isoform of p35), which are two of its neuron-specific regulatory subunits.

It is also worth noting that Cdk5 also regulates the process of apoptosis, which is necessary in order to assure that the neural connections that are formed are correct.

Moreover, because Cdk5 also intervenes in the regulation of synaptic plasticity, it is implicated in the processes of learning and memory formation, as well as the creation of drug addiction.

As a matter of fact, four members of a consanguineous Israeli Muslim family that suffered from lissencephaly-7 with cerebellar hypoplasia had a splice site mutation in the Cdk5 gene.

[14] Upon repetitive administration, several components of dopamine signalling are modified, including changes in gene expression and the circuitry of dopaminoceptive neurons.

Further analysis of the relationship between Cdk5 proportion and drug effects has shown that there is a strong dependence on the dose and frequency of administration.

For example, it has been proved that sustained administration of Cdk5 antagonists inhibits the growth of spiny dendrites in the nucleus accumbens, which could be an avenue for addiction management.

Even though the main role of Cdk5 is related to neuronal migration, its impact on the human body is not limited to the nervous system.

Actually, this enzyme has been found in pancreatic β cells and has been proven to reduce insulin exocytosis by phosphorylating L-VDCC (L-type voltage-dependent Ca2+ channel).

[16] During T-cell activation, Cdk5 phosphorylates coronin 1a, a protein that contributes to the process of phagocytosis and regulates actin polarization.

[20] Several neuronal processes: pain signalling, drug addiction, behavioural changes, the formation of memories and learning, related to the development of the brain, derive from rapid modifications in cytoskeleton.

A negative remodelling of neuronal cytoskeleton will be associated with a loss of synapses and neurodegeneration in brain diseases, where the Cdk5 activity is deregulated.

[21][22] In the laboratory, Cdk5 was blocked in the SCN (suprachiasmatic nuclei, a master oscillator of the circadian system), consequently the free-running period in mice was reduced.

In addition to all the roles previously mentioned, the Cdk5 is involved in numerous cellular functions such as cell mobility survival, apoptosis, and gene regulation.

The chemical explanation of a wide variety of neurological disorders lead to the Cdk5; the abnormal phosphorylation of tau is a pathological action carried out by this kinase and the neurofibrillary tangles are the consequences.

[39] Furthermore, Cdk5 has been reported to be involved in T cell activation and play an important role in development of autoimmune disorders, such as multiple sclerosis.