Inhibiting many individual steps implicated in augmenting excitotoxic induction (e.g., blocking mGluR1, AMPAR, or KAR activation), or downstream in amplifying or expressing excitotoxicity has been demonstrated to be neuroprotective in animal stroke models, but taking such selective targeting forward into the clinic bears significant risk of being bypassed by concurrent unblocked pathways, especially given the huge variability of human stroke presentations. The gene discussed is GRM1; the disease is Stroke.