ERN1 and brain ischemia: It has been summarized that using Sig-1R ligands efficiently reduced the mRNA and protein expression of p-IRE1α suffering from prolonged and severe ER stress following cerebral ischemia injury; meanwhile, expression of p-IRE1α were significantly increased in (Sig-1R-KO)-BCCAO mice (Morihara et al., 2018; Zhao et al., 2019).