For example, the ALS-linked VAPB variant interacts with and inhibits ATF6 transcriptional activity (Gkogkas et al., 2008) and IRE1- and XBP1-mediated signaling activity, and ultimately influences cell susceptibility to ER stress (Kanekura et al., 2006; Suzuki et al., 2009). Here, XBP1 is linked to amyotrophic lateral sclerosis.