Although the actual quantity of CDKL5 required to achieve therapeutic efficacy is not known, we recently demonstrated, using a protein substitution therapy approach with a TATk-CDKL5 fusion protein [22], that the amount of CDKL5 protein necessary to rescue neurological phenotypes of a mouse model of CDD is very small [22]. This evidence concerns the gene CDKL5 and craniodiaphyseal dysplasia.