Initial studies have suggested that presenilin-1 possibly inhibits IRE1 function (Katayama et al., 1999; Niwa et al., 1999), while XBP1 promoter polymorphism has been indicated as an AD risk factor (Liu et al., 2013) and for the development of bipolar disorders and schizophrenia in a genetic association study (Kakiuchi et al., 2003). Here, ERN1 is linked to Alzheimer disease.