CDK5RAP2

CDK5RAP2, also known as CDK5 regulatory subunit-associated protein 2 or CEP215, is a large centrosomal protein encoded by the CDK5RAP2 gene in humans. The protein localizes to the pericentriolar material of centrosomes and is expressed in many cell types, with prominent roles during cell division.

CDK5RAP2 participates in centrosome maturation and microtubule nucleation. It helps recruit and stabilize the gamma-tubulin ring complex at the centrosome and contributes to proper spindle assembly and orientation. Through these actions, it supports accurate mitotic progression and centriole duplication.

Mutations in CDK5RAP2 cause autosomal recessive primary microcephaly (MCPH3), a neurodevelopmental disorder characterized by reduced brain size and, in many cases, intellectual disability. The phenotype is attributed to impaired neural progenitor proliferation during fetal brain development, linked to centrosome dysfunction and mitotic errors.

CDK5RAP2 is a large coiled-coil protein that localizes to the centrosome throughout the cell cycle. It interacts with gamma-tubulin complex components and other centrosomal factors to organize the microtubule organizing center, with conserved functions across vertebrates.

Model systems such as mice and zebrafish bearing CDK5RAP2 mutations recapitulate aspects of centrosome dysfunction and neurodevelopmental defects, supporting its role in brain development. Ongoing research investigates its molecular interactions and contribution to neural progenitor pool maintenance.