Oppositely, USP17 is reported as a deubiquitinase to enhance SETD8 stability.[29] In this study, we discovered that SUMOylation is a novel regulation of SETD8 stability in bladder tumor cells by utilizing our unbiased ProSRSA screening system.[16] Further, we identified that the SUMOylation E3 ligase PIAS1 and the deSUMOylation enzyme SENP6 control this process. Here, KMT5A is linked to urinary bladder neoplasm.