N-methyl-D-aspartate receptor subunit 2D (GluN2D) (GluN2D)

The N-methyl-D-aspartate receptor subunit 2D (GluN2D) is a critical component of a subset of NMDA receptors, which are heterotetrameric ligand-gated ion channels essential for excitatory neurotransmission and synaptic plasticity in the central nervous system [1, 2]. GluN2D-containing receptors are characterized by unique biophysical properties, including exceptionally slow deactivation kinetics, low channel open probability, and reduced sensitivity to magnesium blockade compared to other NMDA receptor subtypes [18, 19]. While widely expressed during embryonic development, GluN2D expression in the adult brain is largely restricted to specific regions such as the basal ganglia and is predominantly localized on GABAergic interneurons [6, 14, 20]. This cell-type specific distribution makes GluN2D a key regulator of inhibitory circuit tone and network oscillations, such as gamma-band power [14]. Dysregulation of GluN2D is implicated in several neurological and psychiatric conditions; gain-of-function mutations in the GRIN2D gene cause severe developmental and epileptic encephalopathy (DEE), while GluN2D hypofunction is linked to schizophrenia and depression [2, 4, 18]. Pharmacological targeting of GluN2D, including the use of selective positive allosteric modulators (PAMs) or antagonists like ketamine—which shows a preference for GluN2D-containing receptors on interneurons—represents a promising therapeutic strategy for restoring excitation-inhibition balance in the brain [6, 7, 13].

Other names

GRIN2DNR2DNMDAR2DGlutamate receptor ionotropic NMDA 2DGluN2D subunitGlutamate ionotropic receptor NMDA type subunit 2D

Antagonist, positive allosteric modulator (PAM), negative allosteric modulator (NAM), and uncompetitive channel blocker.