Glutamate receptor 2

Glutamate receptor 2 (GluR-2, encoded by GRIA2) is an ionotropic glutamate receptor functioning as a ligand-gated cation channel activated by L-glutamate and AMPA-class agonists (UniProt: P42262). The receptor converts glutamatergic signals into electrical impulses by opening its channel upon agonist binding, allowing sodium and calcium influx. GluR-2 participates in fast excitatory synaptic transmission throughout the central nervous system and is involved in receptor trafficking via interactions with NSG1, GRIP1, and STX12 (UniProt: P42262).

GluR-2 is associated with neurodevelopmental disorder with language impairment and behavioral abnormalities (NEDLIB, MIM 618917), characterized by developmental delay, speech impairment, autism spectrum features, and seizures (UniProt: P42262). The protein plays a critical role in glutamatergic neurotransmission, making it relevant to multiple neurological conditions.

In Alzheimer's disease, GluR-2 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). Human proteomic analysis using TMT-labeled mass spectrometry detected a mean log2 fold-change of −0.58, indicating reduced expression across the measured subcellular fractions (Chaparral AD proteomics). This downregulation may contribute to impaired glutamatergic signaling observed in AD pathology.