Bladder cancer (BLCA) is a highly heterogeneous malignancy that develops via a complex multistep biological process. Accumulating evidence has demonstrated the crucial role of the UPR in the progression and outcome of various types of cancer, including BLCA [12, 18, 19]. The UPR was mainly mediated by three ER transmembrane protein sensors: inositol requiring kinase 1 (IRE1), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) [20]. Here, ERN1 is linked to cancer.