Wolframin protein is involved in the suppression of ER stress-induced cell apoptosis by negatively regulating ATF6α and the unfolded protein response (UPR) pathway [17], raising the possibility that the p.W690fsX706 mutant may lose its negative regulation of the ER stress pathway, thereby inducing cell apoptosis and Wolfram syndrome. Here, WFS1 is linked to Wolfram syndrome.