One of themost dysregulated substrates is PDZ and LIM domain protein 7 (PDLIM7).Interestingly, compared to the WT enzyme, the OGA mutant more favorablyremoved the O-GlcNAc modification from PDLIM7 protein, significantlyreduced the level of p53 tumor suppressor and elevated actin-richmembrane protrusions to promote cancer cell motility and aggressiveness. These findings illuminate the critical roleof a stalk domain mutation in dysregulating OGA’s substratespecificity to promote cell malignant progression, opening new opportunitiesfor chemical biology development in anticancer research. Here, PDLIM7 is linked to cancer.