Of the mutations classically associated with adult-onset diabetes [1], [3], curiously, proinsulin-F(B24)S exhibits a more perturbed distal B-chain structure (Figure S3), a twofold decrease in insulin yield from the chain-assembly assay, a partial defect for secretion (Figure S1A), partial engagement in disulfide-linked protein complexes in the ER (Fig. 1), a partial dominant-negative effect on insulin production (Fig. 3), partial recruitment of wild-type proinsulin into disulfide-linked complexes (Fig. 5B), and partial activation of ER stress response (Fig. 8A). The gene discussed is INS; the disease is type 2 diabetes mellitus.