GRIA2 and amyotrophic lateral sclerosis: This behaviorally and pathologically ALS-like phenotype of AR2 mice results from excess influx of Ca2+ through AMPA receptor complexes containing Q/R site-unedited GluA2 subunits20, 21; continuous Ca2+ influx through these abnormal AMPA receptors activates the Ca2+-dependent cysteine protease calpain, which cleaves TDP-43 into aggregation-prone fragments that serve as seeds for TDP-43 pathology20, 21, 22.