Western blot analysis revealed that UCHL5 upregulated ZRANB1 and downregulated SLC7A11/GPX4 expression.<h4>Conclusion</h4>This study demonstrates that UCHL5 acts as a critical tumor suppressor in thyroid cancer by stabilizing ZRANB1 through deubiquitination and regulating ferroptosis via the SLC7A11-GPX4 axis. Here, GPX4 is linked to neoplasm.