ERN1 and amyotrophic lateral sclerosis: Although a recent study reported that inhibition of IRE1 reduced poly(GR)-mediated neurotoxicity in iPSC-derived neurons from C9ALS/FTD patients (62), our findings are consistent with two independent reports demonstrating that enforced expression of Xbp1s attenuated disease progression in models of C9orf72-associated ALS/FTD (50, 51).