Usp35, a member of the deubiquitinases family, is associated with cell proliferation, mitosis, and various biological pathways. It plays significant roles in maintaining protein stability through deubiquitination, thereby influencing multiple cellular processes and disease-related pathways [1,2,3,4,5,6,7,8,9,10].

In lung cancer, Usp35 knockdown promotes ferroptosis, inhibits cell growth, colony formation, and tumor progression, while overexpression reduces erastin/RSL3-triggered ferroptosis. Usp35 directly interacts with ferroportin (FPN) to maintain its protein stability [1]. In ovarian cancer, silencing Usp35 reinforces the activation of the STING-TBK1-IRF3 pathway and promotes type I interferon expression, and knockdown also sensitizes cells to cisplatin [2]. In hepatocellular carcinoma (HCC), Usp35 knockdown decreases the protein level of ABHD17C, impairs the PI3K/AKT pathway, and represses HCC development in vivo [3]. In renal clear cell carcinoma, Usp35 silencing leads to increased cellular apoptosis and sensitivity to ferroptosis, and attenuates xenograft formation [7].

In conclusion, Usp35 is crucial in multiple biological processes and diseases, especially in cancer. Its functions in promoting tumor cell survival, regulating cell death, and influencing metabolic and immune-related pathways are revealed through gene-knockout or knockdown models. These findings provide potential therapeutic targets for cancers such as lung, ovarian, HCC, and renal clear cell carcinoma [1,2,3,7].