The sensor inositol-requiring enzyme 1 alpha (IRE1α) plays a crucial role in diabetes-mediated microvascular injury, mainly by promoting splicing of X-Box Binding Protein 1 (XBP1), further accelerating the degradation of intracellular Vascular Endothelial Growth Factor A (VEGF) and thus interrupting vascular regeneration (reviewed in [18]). The gene discussed is XBP1; the disease is diabetes mellitus.