In this study, we present evidence that MYT1L haploinsufficiency is sufficient to cause phenotypes associated with NDDs and ASD in human neurons as well as in mouse models due to failure to repress target genes resulting in (i) delays during developmental neurogenesis and (ii) synaptic malfunction in mature neurons. MYT1L deficiency in our human and mouse models caused significant deregulation of genes associated with epilepsy, schizophrenia, and ASD, which have been diagnosed in patients carrying MYT1L mutations [13–16]. This evidence concerns the gene MYT1L and epilepsy.