The role of NOTCH2NL genes in human brain development and their involvement in 1q21.1 CNVs associated with a wide variety of neurological disorders emphasizes the importance of the discoveries we describe here: Even if the driving forces of the observed evolutionary changes lie outside the brain, the recent and ongoing structural evolution of human NOTCH2NL genes suggests that the tightly coordinated process of human cortical neurogenesis is still subject to fine-tuning. This evidence concerns the gene NOTCH2NLA and nervous system disorder.