GRIA4 encodes an AMPA-type glutamate ionotropic receptor that functions as a ligand-gated cation channel mediating fast excitatory neurotransmission in the central nervous system. Upon L-glutamate binding, the receptor undergoes conformational changes leading to cation channel opening, allowing sodium and calcium influx that converts chemical signals to electrical impulses 1. The receptor subsequently desensitizes rapidly, entering a transient inactive state 1. GRIA4 is clinically relevant to multiple neuropsychiatric and systemic disorders. Gain-of-function and loss-of-function variants in GRIA4 and related GRIA subunits (GRIA1-3) cause neurodevelopmental disorders characterized by developmental delay, cognitive impairment, seizures, movement disorders, and hypertonia or hypotonia depending on variant type 23. An intronic GRIA4 variant (rs68081839) was identified as a risk locus for comorbid nicotine dependence and major depression in genome-wide association studies, suggesting shared glutamatergic dysfunction in these psychiatric conditions 4. Additionally, GRIA4 expression is altered in colorectal cancer, with hypermethylation and downregulation observed in >97% of tumors, positioning it as a potential diagnostic biomarker 5. In vascular pathology, GRIA4 participates in a circCBFB/miR-28-5p/GRIA4/LYPD3 regulatory axis controlling vascular smooth muscle cell apoptosis relevant to abdominal aortic aneurysm 6. However, GRIA4 polymorphisms show no significant association with schizophrenia susceptibility or migraine in studied populations 78.