CDKL5 ensures excitatory synapse stability by reinforcing NGL-1–PSD95 interaction in the postsynaptic compartment and is impaired in patient iPSC-derived neurons

The CDKL5 kinase is mutated in several neurodevelopmental disorders. Broccoli and colleagues find that CDKL5 regulates dendritic spine formation by phosphorylating the adhesion molecule NGL-1, which acts on synaptic contacts. They also show that neurons (derived from induced pluripotent stem cells) from patients carrying the CDKL5 mutation have aberrant dendritic spines, similarly to rodents with impaired CDKL5 function.