One of the most notable trends in mammalian evolution is the massive increase in size of the cerebral cortex, especially in primates. Relative brain size differs markedly between species. This variation might ultimately result from differences in the cell biology of neural progenitors, which might underlie their different proliferative potential. What genes, if any, are responsible for a larger brain in humans remains a biological mistery.

Mutations in ASPM (abnormal spindle-like microcephaly associated) cause primary microcephaly in humans, a disorder characterized by a major reduction in brain size in the apparent absence of nonneurological anomalies. Furthermore, ASPM protein is evolutionary conserved with a consistent correlation of nervous-system complexity and Aspm protein length, leading to the hypothesis that AspM is the molecuylar determinant of brain size (Bond et al. 2002).