While mounting evidence suggests that BiP activity is linked to neurodegenerative diseases, diabetes, cardiovascular diseases, cancer progression and anticancer drug resistance, (Schönthal, 2013; Dudek et al., 2009) these tunable properties of the BiP conformational landscape are particularly interesting because they potentially provide new opportunities to develop BiP-specific allosteric drugs (Nussinov and Tsai, 2013) to enable precise modulations of BiP activity. Here, HSPA5 is linked to diabetes mellitus.