Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:9489750, PubMed:27616483, PubMed:26875626, PubMed:28126851). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:9489750). Heterotetramer. Forms heterotetrameric channels composed of two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) (in vitro) (PubMed:9489750, PubMed:26875626, PubMed:28126851). In vivo, the subunit composition may depend on the expression levels of the different subunits (Probable). Interacts with PDZ domains of PATJ and DLG4 (By similarity). A hydrophobic region that gives rise to the prediction of a transmembrane span does not cross the membrane, but is part of a discontinuously helical region that dips into the membrane and is probably part of the pore and of the selectivity filter. The disease is caused by variants affecting the gene represented in this entry. Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2D/GRIN2D subfamily.