Mediates thiol-dependent retention in the early secretory pathway, forming mixed disulfides with substrate proteins through its conserved CRFS motif (PubMed:11847130, PubMed:14517240). Inhibits the calcium channel activity of ITPR1 (PubMed:15652484). May have a role in the control of oxidative protein folding in the endoplasmic reticulum (PubMed:11847130, PubMed:29858230, PubMed:14517240). Required to retain ERO1A and ERO1B in the endoplasmic reticulum (PubMed:11847130, PubMed:29858230). Forms mixed disulfides with both ERO1A and ERO1B and cargo folding intermediates; the interactions with ERO1A and ERO1B result in their retention in the endoplasmic reticulum (PubMed:11847130, PubMed:29858230). Directly interacts with ITPR1 in a pH-, redox state- and calcium-dependent manner, but not with ITPR2 or ITPR3 (PubMed:15652484). The strength of this interaction inversely correlates with calcium concentration (By similarity). Up-regulated by inducers of the unfolded protein response (UPR), including tunicamycin and dithiothreitol.