PTEN and Nephropathy: 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