Gria2, also known as Glutamate receptor, ionotropic, AMPA2 (alpha 2), encodes the GluA2 subunit of the AMPA receptor. AMPA receptors are tetrameric ligand-gated channels, and GluA2 is crucial as post-transcriptional editing at the Q607 site renders heteromultimeric AMPARs Ca2+-impermeable. This gene is involved in glutamatergic synaptic transmission, which is vital for normal brain function [2].

In lower extremity artery restenosis after percutaneous transluminal angioplasty (PTA), GRIA2 is highly differentially expressed in restenotic arterial plaques. Overexpression of GRIA2 promotes the proliferation and migration of vascular smooth muscle cells (VSMCs) through upregulation of ENPP3, suggesting its role in restenosis development [1].

In neurodevelopmental disorders, de-novo heterozygous mutations in GRIA2 have been found in patients with intellectual disability, autism spectrum disorder, Rett syndrome-like features, and seizures. Functional expression studies show that these mutations decrease agonist-evoked current mediated by mutant subunits [2]. A novel gain-of-function GRIA2 variant has been associated with neurodevelopmental delay and seizures, and the antiseizure drug perampanel was effective in treating the patient [7]. Also, in a patient with atypical autism spectrum disorder, a de novo GRIA2 variant was reported, expanding the phenotypic variation spectrum [3].

In methamphetamine-use disorder, serum GRIA2 is higher in patients, and miR-181a negatively regulates GRIA2 expression [5].

In Dazu Black Goats, SNPs in GRIA2 are associated with reproductive traits [6]. GRIA2 is also a useful diagnostic marker for solitary fibrous tumour [4].

In conclusion, Gria2 plays essential roles in multiple biological processes and disease conditions. Its functions in the nervous system related to synaptic transmission and in non-neural tissues such as in vascular smooth muscle cell regulation in restenosis, as well as its associations with various disorders like neurodevelopmental disorders, autism spectrum disorder, methamphetamine-use disorder, and reproductive traits in goats, are significant. Research on Gria2 using genetic models could potentially provide more insights into these disease mechanisms and lead to better treatment strategies.