The inherently lower Ca2+ buffering of ALS-sensitive MNs is aggravated by high expression of Ca2+-permeable AMPA receptors (AMPAR) comprising the unedited glutamate receptor 2 (GluR2) subunit (Grosskreutz et al. 2010; Van Den Bosch et al. 2006; Greig et al. 2000; Zanganeh et al. 2022) (Fig. 2). With over 1/3 of AMPAR being permeable for Ca2+, the larger Ca2+ influx strains the ER and mitochondrial calcium buffering of MNs and increases the risks of cell stress and degeneration (Greig et al. 2000). This evidence concerns the gene GRIA2 and amyotrophic lateral sclerosis.