In conclusion, RRBP1 drives tumor malignancy through fusion with ALK or USP6 genes and the RRBP1-ALK fusion might enhance cancer cell survival and invasiveness through ER localization, whereas the RRBP1-USP6 fusion aberrantly activates ubiquitination regulation, thus suggesting an association between ER-ribosome pathway dysregulation and tumor progression. Here, USP6 is linked to neoplasm.