NR2D

NR2D is a subunit of NMDA-type glutamate receptors, encoded by the GRIN2D gene in humans. NMDA receptors are ligand-gated ion channels that typically assemble as tetramers containing two NR1 subunits and two NR2 subunits. The NR2 family (NR2A through NR2D) defines receptor properties, including channel kinetics and pharmacology. When NR2D is incorporated into an NMDA receptor, it contributes distinct functional characteristics compared with receptors containing other NR2 subunits.

Expression of GRIN2D is developmentally regulated. During prenatal and early postnatal periods, NR2D-containing receptors are relatively prominent in several brain regions, with expression declining as maturation proceeds. Nevertheless, NR2D-containing receptors persist in certain circuits, including specific thalamic, brainstem, and cortical interneuron populations, contributing to synaptic signaling in those areas.

Functional properties of NR2D-containing NMDA receptors include slower deactivation kinetics and longer-lasting synaptic currents relative to NR2A- or NR2B-containing receptors. This unique kinetic profile supports prolonged excitatory signaling and can influence synaptic plasticity and developmental circuit formation. The pharmacology of NR2D-containing receptors is distinct from other NR2 subtypes, and their activity can be differentially modulated by various ligands and channel blockers.

Clinical relevance: variants in GRIN2D have been associated with neurodevelopmental disorders, including epilepsy and intellectual disability. Because NR2D-containing receptors play roles in developmental synaptic maturation and network excitability, they are of interest as potential targets for therapeutic strategies in neurodevelopmental disease and epilepsy. Research continues into selective modulators of NR2D function and their clinical applications.