GRIN1 encodes the obligatory GluN1 subunit of N-methyl-D-aspartate receptors (NMDARs), heterotetrameric ligand-gated calcium channels essential for synaptic transmission 1. GRIN1 functions as a co-agonist binding site for glycine or D-serine; channel activation requires glutamate binding to GluN2 subunits, co-agonist binding to GluN1, and membrane depolarization to relieve Mg2+ block 1. NMDARs mediate calcium and sodium influx while allowing potassium efflux, supporting long-term potentiation and synaptic plasticity underlying learning and memory 1. GRIN1 pathogenic variants cause rare developmental encephalopathies characterized by intellectual disability, developmental delay, autism, and epilepsy 1. Loss-of-function variants account for a significant portion of GRIN-related disorder cases 2. De novo mutations in GRIN1 have been identified in infantile spasms and Lennox-Gastaut syndrome cohorts 3. Additionally, autoantibodies against NMDARs (anti-NMDA receptor encephalitis) cause an autoimmune encephalitis predominantly affecting women, characterized by psychiatric symptoms, cognitive impairment, seizures, and abnormal movements, with 80% of patients improving with immunotherapy 4. L-serine supplementation, a co-agonist for GRIN1, shows promise for GRIN loss-of-function disorders, improving adaptive behavior, motor function, and quality of life in clinical trials 2. Proper GRIN1 expression is regulated by transcription factors including REST, EGR1, and CREB1 in its proximal promoter region 5.