Mutations or heterozygous deletions of PAHFAH1B1/ Lis1 alone causes Isolated Lissencephaly Sequence (ILS), a disorder characterised by reduced neuronal migration resulting in a cortical surface without significant invaginations, effectively a "smooth brain" (lissencephaly) (Fig. 1). The gene discussed is PAFAH1B1; the disease is lissencephaly spectrum disorders.