GRIN3A encodes the GluN3A subunit of N-methyl-D-aspartate (NMDA) receptors, functioning as a component of heterotetrameric, ligand-gated cation channels with low calcium permeability and reduced voltage-dependent magnesium block 1. The protein forms two distinct receptor complexes: conventional glutamatergic receptors with GluN1 and GluN2 subunits activated by glycine and L-glutamate, and excitatory glycinergic receptors (eGlyRs) with GluN1 alone activated by glycine or D-serine 2. During neural development, GluN3A participates in synaptic refinement by restricting spine maturation and growth through competition with GIT1 interaction with ARHGEF7, thereby limiting RAC1 activation at inactive synapses. Each GluN3 subunit confers differential channel properties including activation kinetics, desensitization, and pH sensitivity. Genetic variations in GRIN3A are associated with multiple neuropsychiatric and systemic conditions. A missense variant (p.R480G) shows significant association with schizophrenia 3, while polymorphisms correlate with postpartum depressive symptoms 4 and postoperative delirium 5. GRIN3A variants also associate with coronary artery aneurysm complications in Kawasaki disease 6, cognitive decline in APOE-ε4 carriers 7, and quality of life in methadone maintenance therapy 8. Elevated GRIN3A expression contributes to abnormal nerve proliferation in macrodactyly 9. eGlyRs concentrated in emotional-response-regulating brain regions represent emerging therapeutic targets in neuropsychiatry.