GRIK3 encodes an ionotropic glutamate receptor that functions as a ligand-gated cation channel activated by L-glutamate and kainic acid. Binding of glutamate triggers channel opening and rapid desensitization, converting chemical signals into electrical impulses. In the hippocampus, GRIK3 associates with GRIK2 to facilitate presynaptic glutamate release at mossy fiber synapses. Haploinsufficiency of GRIK3 impairs synaptic potentiation and neurotransmission. A 2.6-Mb microdeletion involving GRIK3 caused severe developmental delay with language and motor deficits 1, and genetic variants show association with recurrent major depressive disorder 2 and delirium tremens in alcoholics 3. Recent evidence suggests GRIK3 plays unexpected roles in non-neuronal contexts: transient GRIK3 expression on rod precursor cells detects light-dependent glutamate signaling from intrinsically photosensitive retinal ganglion cells during visual system development 4. In cancer, aberrant GRIK3 expression promotes proliferation via Src-dependent PDGFRα activation in pilocytic astrocytoma 5 and drives gastric cancer progression through circRNA-miRNA regulatory axes 6, 7. GRIK3 polymorphisms associate with diabetic retinopathy in type 2 diabetes 8. Kainate receptor antagonists including selurampanel and tezampanel represent potential therapeutic approaches for GRIK3-related disorders.