GRIA3 encodes an AMPA-type ionotropic glutamate receptor subunit that mediates fast excitatory neurotransmission in the central nervous system 1. The receptor functions as a ligand-gated cation channel activated by glutamate, which induces conformational changes leading to calcium influx and conversion of chemical signals to electrical impulses 1. GRIA3 is unique among AMPA receptor subunits for being X-chrX located, making it clinically significant for sex-dependent inheritance patterns 1. GRIA3 variants cause diverse neurodevelopmental disorders with distinct phenotypes depending on functional consequence: loss-of-function variants associate with hypotonia, older seizure onset (median 16 months), and sleep disturbances, while gain-of-function variants cause hypertonia, earlier seizure onset (median 1 month), and movement disorders including hyperekplexia 1. Ultra-rare coding variants in GRIA3 confer substantial schizophrenia risk (odds ratios 3-50), supporting glutamatergic system dysfunction as a pathogenic mechanism 2. GRIA3 variants are implicated in developmental and epileptic encephalopathy 3, with clinical presentation ranging from seizures to developmental encephalopathy without seizures 1. The gene's role in excitatory synaptic transmission and long-term potentiation underlies its involvement in intellectual disability and neurodevelopmental phenotypes 1.