Glutamate receptor ionotropic NMDA 2D (GRIN2D) (GRIN2D)

The Glutamate receptor ionotropic NMDA 2D (GRIN2D), also known as GluN2D, is a protein subunit that forms part of the N-methyl-D-aspartate (NMDA) receptor complex, a critical ligand-gated ion channel in the central nervous system (UniProt: Q15399). NMDA receptors are typically heterotetramers composed of two glycine-binding GluN1 subunits and two glutamate-binding GluN2 subunits; the GluN2D subunit is distinguished by its slow deactivation kinetics and reduced sensitivity to magnesium blockade compared to other subunits (PubMed: 25131155). It is predominantly expressed in the basal ganglia, thalamus, and brainstem, playing a vital role in the development of neural circuits and the modulation of motor and cognitive functions (GeneCards: GRIN2D). Mutations in the GRIN2D gene are associated with severe neurodevelopmental disorders, including developmental and epileptic encephalopathy, while its dysfunction is implicated in schizophrenia and Parkinson's disease (PubMed: 31433458). Therapeutic strategies targeting GRIN2D involve both non-selective NMDA antagonists like ketamine and memantine, as well as experimental subtype-selective modulators designed to treat movement disorders and psychiatric symptoms with improved safety profiles.

Other names

GluN2DNR2DNMDAR2DGlutamate [NMDA] receptor subunit epsilon-4EBPGluR epsilon-4

Non-competitive antagonism via pore blockade and allosteric modulation of the ion channel to regulate the influx of calcium and sodium ions in response to glutamate and glycine binding.