We discuss the clinical features of MCPH, parallels between human and <i>Drosophila</i> neurogenesis modes with a particular focus on the fly optic lobe, and highlight four of the most well-studied <i>Drosophila</i> MCPH orthologs: <i>abnormal spindle (asp)/MCPH5, Microcephalin/MCPH1, WD Repeat-Containing Protein 62 (Wdr62)/MCPH2</i>, and <i>Ankryin Repeat-and LEM Domain- Containing Protein 2 (ANKLE2)</i>/<i>MCPH16</i>. This evidence concerns the gene ANKLE2 and autosomal recessive primary microcephaly.