The oxidoreductase ERO1 (endoplasmic reticulum [ER] oxidoreductin 1) is thought to be crucial for disulfide bond formation in the ER. In this issue, Zito et al. (2010. J. Cell Biol. doi:10.1083/jcb.200911086) examine the division of labor between the two mammalian isoforms of ERO1 (ERO1-alpha and -beta) in oxidative folding. Their analysis reveals a selective role for ERO1-beta in insulin production and a surprisingly minor contribution for either ERO1 isoform on immunoglobulin folding and secretion.