The X-box-binding protein-1 (XBP1), spliced and activated by IRE1α, is downregulated in glomerular mesangial cells, weakening the inhibitory effect on the phosphatase and tensin homolog (PTEN)/Akt pathway, thereby aggravating kidney damage.60 ERS also contributes to DPN and DR, with increased IRE1 in the neurons,61 and upregulated CHOP, caspase 12, and phosphorylated JNK in diabetic retina.62 The gene discussed is ERN1; the disease is Nephropathy.