Besides interacting with Lis1 physically, the CNS and cerebral cortical specific role of Nde1 was further demonstrated by the recent identification of NDE1 recessive mutations in humans, which showed that loss of NDE1 function resulted in extreme microcephaly (small brain) and lissencephaly, and that the affected individuals had brains less than 10% of expected size and defective cortical lamination [16],[17]. This evidence concerns the gene PAFAH1B1 and lissencephaly spectrum disorders.