In a previous study, we found that C2C12 mouse skeletal muscle cells overexpressing the P56S-missense mutated vesicle-associated membrane protein/synaptobrevin-associated membrane protein (VAPB), which is the causative gene of familial amyotrophic lateral sclerosis (ALS) [29], exhibit marked myotube formation disruption and IRE1 activation inhibition [30]; this suggests that IRE1 positively controls myogenic differentiation as well as other UPR-sensor factors. Here, ERN1 is linked to amyotrophic lateral sclerosis.