USP22 and neoplasm: In addition, estrogen signaling modulates ATXN7L3’s function, potentially switching HCC from a tumor-promoting to a tumor-suppressing state by facilitating deubiquitinase swapping, where ATXN7L3 and ENY2 replace USP22 (a tumor-promoting deubiquitinase) with USP27x or USP51 (potential tumor-suppressing deubiquitinases) (40).