Notably, Wolfram Syndrome, also known as DIDMOAD (diabetes insipidus, insulin-deficient diabetes mellitus, optic atrophy, and deafness), has been strongly associated with significant disruptions in endoplasmic reticulum functionality (Figure 7B, “protein processing in endoplasmic reticulum”), membrane trafficking (Figure 7B, “endocytosis”), and calcium homeostasis (Krey and Dolmetsch, 2007). The gene discussed is INS; the disease is Leber hereditary optic neuropathy.