GRIN2B encodes the N-methyl-d-aspartate receptor (NMDAR) subunit GluN2B. NMDARs are ionotropic receptors that form cation channels in nerve cells, which require binding of glutamate and glycine for activation. They are heteromeric complexes composed of two obligatory GluN1 subunits and two additional GluN2 (GluN2A-D) or GluN3 subunits. NMDARs have critical roles in synaptic plasticity and neuronal development. NMDAR dysfunction, as a result of de novo mutations, is associated with severe neurodevelopmental delay. Mutations in GRIN2B have been continuously and increasingly reported from whole-exome sequencing of patients with neurodevelopmental disorder (~300 cases worldwide) in the past several years. Newly synthesized GRIN2B gene products are inserted into endoplasmic reticulum (ER) for proper folding and assembly. Only proteins that are correctly folded and assembled or that pass ER protein quality control checkpoint are exported from the ER to neuronal plasma membrane for its function. To understand the consequences of GRIN2B mutations on the channel function, investigators have been focusing on studying biophysical properties of NMDAR. While the functional analysis is critical, biochemical characterization of each mutant is equally essential. From lessons with analyses of cystic fibrosis patients with different mutations on cystic fibrosis transmembrane conductance regulator, we learned that systemic categorization of mutants into subclasses (e.g., protein production mutation`s, protein stability mutations, protein processing mutations, channel gating mutations, trafficking mutations, etc.) is fundamental because different therapeutic approaches must be applied depending on the causes. To gain a full comprehension of the biochemical mechanism of each mutant or the assignment to a functional class, we propose to pursue functional characterization of GRIN2B mutations at biochemical level using cell-based studies.