GRIA1, encoding the GluA1 subunit of α -amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors, is a ligand-gated ion channel gene. AMPA receptors are crucial for excitatory neurotransmission in the brain, and GluA1-containing AMPARs have a vital role in brain function [1,3].

Functional studies on individuals with GRIA1 variants show that both heterozygous and homozygous variants can lead to a neurodevelopmental disorder mainly affecting cognition and speech [3]. For example, the p.(Ala636Thr) variant in GRIA1 is associated with motor and/or language delay, intellectual disability, behavioral and psychiatric comorbidities, hypotonia, and epilepsy [1]. In a Xenopus gria1 CRISPR-Cas9 F0 model, mutants display transient motor deficits, intermittent seizure phenotypes, and significant working memory impairment, supporting the role of GRIA1 in these functions [3]. Also, in rats with cerebral ischemia-reperfusion injury, sevoflurane preconditioning downregulates GRIA1 expression, attenuating neuronal injury, indicating its role in this pathological process [2].

In conclusion, GRIA1 is essential for excitatory neurotransmission in the brain. Research using genetic models like the Xenopus gria1 model and rat models with cerebral ischemia-reperfusion injury has revealed its significance in neurodevelopmental disorders and neuronal injury related to ischemia-reperfusion. Understanding GRIA1 function provides insights into the mechanisms of these conditions and may guide future therapeutic strategies.