Cellular roles of the CDKL5 kinase relevant to CDKL5 deficiency disorder (CDD)

Mutations in the gene encoding the protein kinase CDKL5 can result in a debilitating neurodevelopmental disease termed CDKL5 deficiency disorder (CDD). The development of treatments for CDKL5 disorder has been hampered by a lack of understanding of the molecular basis for the symptoms underlying this disease. This in turn is limited by a lack of understanding of the cellular processes controlled by CDKL5. In most cell types studied to date, CDKL5 is found in both the cytosol and nucleus. We recently identified the first cytoplasmic substrates of CDKL5, which includes cytoskeleton and centrosome regulators and recent data suggess a role for CDKL5 in controlling the microtubule-based cytoskeleton and primary cilia. However, the nuclear substrates remain to be identified. This has a become a pressing issue as my research team has recently uncovered interesting roles for CDKL5 in the nucleus. As well as presenting recent data regarding nuclear CDKL5, I discuss how defects in nuclear functions of CDKL5 could cause CDKL5 disorder and how they could suggest new therapies.