The role of CDKL5 for proper brain development and functioning is still not fully understood, but the combination of in vitro molecular studies on cultured primary neurons with in vivo phenotyping of the generated CDD mouse models has begun to shed light on the physiological functions of CDKL5 and on the etiology of CDD (Zhu and Xiong, 2019). Here, CDKL5 is linked to craniodiaphyseal dysplasia.