Finally, it is essential to note that the Asn-cage residues in GluN2A and GluN2B are susceptible to de novo mutations in humans, which alter voltage-dependent Mg2+ block and are consequently associated with neurological diseases, including autism spectrum disorder, epilepsy, intellectual disability, and developmental delay (Li et al., 2019), indicating the crucial role of the Asn-cage in neuronal functions in brain development. This evidence concerns the gene GRIN2A and Global developmental delay.