The N-methyl-D-aspartate receptor (NMDAR) is a receptor of glutamate, the primary excitatory neurotransmitter in the human brain. NMDA subunits are encoded by GRIN genes. GRIN-related neurodevelopmental disorders (GRIN-NDD) encompass a spectrum of disorders, featuring intellectual disability, behavioural disorders and epilepsy, and are caused by NMDAR dysfunction due to germline pathogenic variants. The estimates for GRIN-NDD incidence range from 122 to 224 per year in the United States. Pathogenic variants in GRIN genes may result in NMDAR gain or loss of function (GoF/LoF). This observation gave rise to the hypothesis of successfully treating GRIN-NDD due to LoF variants with NMDAR co-agonists such as L-serine. The main objective of the study is to validate GRIN LoF variants as targets for treatment with L-serine. We aim to demonstrate that L-serine improves neurodevelopmental outcomes in children and young adults with GRIN-NDD. We will determine global clinical improvements along with changes in cognitive and motor function, behaviour, sleep, and seizures. We will use neurophysiological (EEG and Transcranial Magnetic Stimulation (TMS) combined with EEG) and pre-clinical (variant-specific cellular models including 2D and 3D brain organoids) biomarkers to validate treatment effects. We will use single-patient trials (n-of-1s) to evaluate the clinical effect of L-serine compared to placebo in patients with GRIN-NDD. The aggregation of multiple SPTs will produce a population estimate of the benefit. Patients will complete a minimum of two cycles (6-month each) of treatment. Each cycle will comprise three months of treatment and placebo, the order of which will be randomly allocated for each cycle. Through the aggregation of individual trials, a population estimate of treatment effects along with pre-clinical and clinical biomarkers will be provided to guide clinical practice in the treatment of individuals with GRIN-NDD.