Taken together, our work demonstrated that ACE induces ferroptosis in tumor cells through a dual mechanism: on the one hand, ACE enhances intracellular Fe2+-induced ferroptosis by directly binding and degrading PCBP 1/2, and on the other hand, ACE induces GPX4 ubiquitination and degradation by directly binding to GPX4. Here, GPX4 is linked to neoplasm.