In Wolfram syndrome, absent or reduced levels of wolframin disrupt normal ER functioning, leading to ER stress-induced apoptosis (Takeda et al., 2001; Ishihara et al., 2004; Fonseca et al., 2005; Riggs et al., 2005; Yamada et al., 2006; Akiyama et al., 2009; Fonseca et al., 2009; Fonseca et al., 2010). This evidence concerns the gene WFS1 and Wolfram syndrome.