Sigma-1 receptor (Sigmar1) is an ER-resident chaperone that regulates IRE1 function (Hayashi and Su, 2007; Mori et al., 2013), and that can be targeted through high-affinity agonists including fluvoxamine, an antidepressant that prevents IRE1-dependent hyperinflammation in sepsis models (Rosen et al., 2019). This evidence concerns the gene ERN1 and Sepsis.