INS and diabetes mellitus: The pathophysiological significance of inefficient PPI translocation is highlighted by recent evidence showing that deficiency of TRAPα [translocon associated protein alpha, a type 2 diabetes associated gene (8)], TRAPβ, and/or TRAPδ impairs PPI translocation and insulin production (9, 10), and also by the discoveries of PPI SP mutations that impair PPI translocation causing β-cell failure and diabetes in humans (2, 11–14).