Amyotrophic lateral sclerosis (ALS) patients show increased PERK, ATF6, and IRE1 signaling, with higher levels of CHOP and BiP in the spinal cord [84], and increases in downstream elements of the UPR such as ATF4, XBP-1, and GRP58 [85]. Here, ERN1 is linked to amyotrophic lateral sclerosis.