Subunit-selective agents now dominate therapeutic innovation: GluN2B-selective antagonists (e.g., ifenprodil and its derivatives) preferentially target neurodegenerative extrasynaptic receptors without impairing cognition in AD and HD models (Ugale et al., 2024), while GluN2A-positive allosteric modulators (PAMs) counteract synaptic depletion in late-stage disease (Yukawa et al., 2023). This evidence concerns the gene GRIN2B and Alzheimer disease.