Notably, knockdown of ENY2 in p53-mutant cancer cell lines exhibits an augmented binding affinity and silencing efficacy of RISC towards target mRNA molecules, ultimately suppressing tumor proliferation through a p53-independent manner.<h4>Conclusions</h4>This study elucidated a previously unrecognized role of ENY2 in tumor growth, clarified the NPM1/MDM2/ p53-dependent mechanism of ENY2-mediated tumor cell growth suppression. Here, NPM1 is linked to neoplasm.