This study investigates the role of CYLD, a novel deubiquitinating enzyme, in prostate cancer (PCa) progression. The authors found that CYLD expression is downregulated in PCa tissues and is inversely correlated with pathological grade and clinical stage. CYLD was shown to inhibit tumor cell proliferation and enhance sensitivity to ferroptosis in both in vitro and in vivo models of PCa. Mechanistically, CYLD suppresses the ubiquitination of YAP protein, promoting the transcription of ACSL4 and TFRC genes. The study also demonstrated that CYLD enhances the sensitivity of PCa xenografts to ferroptosis and that there is a positive correlation between CYLD expression and ACSL4 or TFRC expression in human PCa specimens. These findings suggest that CYLD acts as a tumor suppressor gene in PCa and promotes cell ferroptosis through the Hippo/YAP signaling pathway.This study investigates the role of CYLD, a novel deubiquitinating enzyme, in prostate cancer (PCa) progression. The authors found that CYLD expression is downregulated in PCa tissues and is inversely correlated with pathological grade and clinical stage. CYLD was shown to inhibit tumor cell proliferation and enhance sensitivity to ferroptosis in both in vitro and in vivo models of PCa. Mechanistically, CYLD suppresses the ubiquitination of YAP protein, promoting the transcription of ACSL4 and TFRC genes. The study also demonstrated that CYLD enhances the sensitivity of PCa xenografts to ferroptosis and that there is a positive correlation between CYLD expression and ACSL4 or TFRC expression in human PCa specimens. These findings suggest that CYLD acts as a tumor suppressor gene in PCa and promotes cell ferroptosis through the Hippo/YAP signaling pathway.