GRIN2C encodes the GluN2C subunit of N-methyl-D-aspartate receptors (NMDARs), heterotetrameric ligand-gated cation channels with high calcium permeability 12. Channel activation requires L-glutamate binding to GluN2C, glycine/D-serine binding to GluN1, and membrane depolarization to relieve Mg2+ blockade 12. GluN2C confers unique kinetic properties including activation, deactivation, and desensitization rates 1. The subunit mediates potassium efflux and calcium/sodium influx, participating in synaptic plasticity, learning, and long-term potentiation. GluN2C expression is dynamically regulated by histone methyltransferase EZH2, with demethylase inhibition reducing its expression in developing neurons 34. Disease-relevance is emerging: a rare missense variant (A1072V) segregates with familial late-onset Alzheimer's disease, increasing NMDAR-mediated currents and surface expression 5. GluN2C variants appear less pathogenic than GluN2A/2B truncations in neurodevelopmental disorders 6, though frameshift mutations associate with schizophrenia susceptibility 7. Mendelian randomization studies identify increased GluN2C expression as a risk factor for depression 8, suggesting therapeutic targeting potential for mood disorders.