Alternatively, PDIA1 may reduce improper proinsulin disulfide bonds as demonstrated during infection with pathogens that require reduction for retro-translocation from the ER to the cytosol (Tsai et al., 2001; Inoue et al., 2015) and from evidence that supports a role for PDI as a reductase important for degradation of mutant Akita proinsulin (He et al., 2015) and mutant thyroglobulin (Forster et al., 2006). This evidence concerns the gene P4HB and infection.