Notch homolog 2 N-terminal-like is a protein that in humans is encoded by the NOTCH2NLgene. It appears to play a key role in the development of the brain.
NOTCH2NL increases the number of corticalstem cells, which while delaying the generation of neurons ultimately leads to a greater number of neurons and larger brains. NOTCH2NL copy number loss and gain is associated with various neurological disorders, and they showed that loss of NOTCH2NL in human minibrains organoids leads to the organoids being smaller, while resulting in premature differentiation of cortical stem cells into neurons. The role of NOTCH2NL in the development of the human brain together with the evolutionary history of NOTCH2NL genes, suggests that the emergence of NOTCH2NL genes may have contributed to the increase in size of the human neocortex which tripled over the last two million years.