Cdkl5, or cyclin-dependent kinase-like 5, is a serine-threonine kinase highly expressed in the developing brain [2]. It regulates key phosphorylation events vital to the development of the brain's complex neuronal network [1]. It has been found to be involved in pathways such as virophagy, where it regulates p62-mediated selective autophagy against neurotropic viruses [3]. Loss-of-function mutations in Cdkl5 are associated with CDKL5 deficiency disorder (CDD), a severe X-linked brain disorder [1,2].

In Cdkl5-knockout mice, increased viral antigen accumulation, neuronal cell death after infection with neurotropic viruses, and enhanced lethality were observed, indicating its role in antiviral immunity through regulating virophagy [3]. Acute ablation of Cdkl5 from adult forebrain glutamatergic neurons in mice led to elevated neural network activity in the dentate gyrus and early-onset spontaneous seizures via TrkB signaling, suggesting its importance in maintaining normal neural network activity and preventing epileptogenesis [4].

In conclusion, Cdkl5 is crucial for normal brain development and function, especially in maintaining neuronal network stability and antiviral immunity. Studies using Cdkl5 knockout mouse models have revealed its significant roles in CDD-related epileptogenesis and antiviral response, providing insights into the disease mechanisms and potential therapeutic targets for CDD.