GRIN2A encodes the GluN2A subunit of N-methyl-D-aspartate (NMDA) receptors, heterotetrameric ligand-gated cation channels with high calcium permeability and voltage-dependent magnesium block 1. Channel activation requires L-glutamate binding to GluN2A, glycine/D-serine binding to GluN1, and membrane depolarization to relieve Mg2+ inhibition 2. GluN2A confers distinct kinetic properties including differential activation, deactivation, desensitization, pH sensitivity, and calcium permeability 3. NMDA receptors mediate synaptic plasticity underlying learning and memory through long-term potentiation 2. GRIN2A dysfunction is implicated in schizophrenia through both common and rare variants 45. Ultra-rare coding variants confer substantial schizophrenia risk (odds ratios 3-50), supporting glutamatergic system dysfunction in pathogenesis 4. Common variants concentrate in genes expressed in central nervous system neurons 5. Pathogenic GRIN2A variants cause developmental and epileptic encephalopathy with speech-language features 6. Transmembrane domain missense variants typically produce gain-of-function effects and severe phenotypes, while amino-terminal/ligand-binding domain variants and null mutations cause loss-of-function with milder phenotypes 6. L-serine treatment shows therapeutic promise for loss-of-function variants, improving adaptive behavior, motor function, and quality of life in children 7. GRIN2A variants demonstrate overlap with autism, epilepsy, and neurodevelopmental disorders, revealing convergence of common and rare variant pathways 4.