16F16, a protein disulfide bond isomerase (PDI) inhibitor, was first identified in a screen for compounds that screen Huntington protein-induced apoptosis. 16F16 not only inhibited apoptosis induced by the misfolded protein mutant Huntington gene, but also protected rat neurons from Aβ peptide-induced cell death. This inhibitor action helps to identify a novel mechanism in which the cell death pathway is regulated by protein misfolding through PDI upregulation. 16F16, a protein disulfide bond isomerase (PDI) inhibitor, was first identified in a screen for compounds that screen Huntington protein-induced apoptosis. 16F16 not only inhibited apoptosis induced by the misfolded protein mutant Huntington gene, but also protected rat neurons from Aβ peptide-induced cell death. This inhibitor action helps to identify a novel mechanism in which the cell death pathway is regulated by protein misfolding through PDI upregulation.