Usp36, a member of the USP family of deubiquitinating enzymes, plays a crucial role in the balance between ubiquitination and deubiquitination by hydrolyzing and removing ubiquitin chains from target proteins, thus regulating protein stability and maintaining cellular homeostasis. It is involved in various cellular events such as gene transcription regulation, cell cycle regulation, and signal transduction, and is associated with multiple disease processes including cancer, infections, and inflammation [7].

In cancer research, studies have shown diverse functions of Usp36. In solid tumors, ribotoxic stress activates the JNK-Usp36 signaling to stabilize Snail1 in the nucleolus, facilitating ribosome biogenesis and tumor cell survival, and also contributing to solid tumor cell resistance to the ribosome inhibitor homoharringtonine (HHT) [1]. In breast cancer, Usp36 promotes tumorigenesis and tamoxifen resistance by deubiquitinating and stabilizing ERα [2]. In colorectal cancer, knockdown of Usp36 induces apoptosis as it deubiquitinates cIAP1 and survivin to inhibit their degradation, and it also promotes cancer progression through inhibition of the p53 signaling pathway via stabilizing RBM28 [3,4]. In glioblastoma, Usp36 stabilizes ALKBH5 to promote tumorigenesis, and its depletion sensitizes glioma stem cells to temozolomide treatment [5]. In esophageal squamous carcinoma, Usp36 facilitates cancer progression by stabilizing YAP [6]. In non-small cell lung cancer, a germline mutation in Usp36 confers resistance to EGFR-TKIs by upregulating MLLT3 expression [8].

In conclusion, Usp36 is a key regulator in multiple cellular processes and is significantly involved in cancer development and drug resistance. The findings from various in vivo and functional studies, though not always from KO/CKO mouse models in the provided references, have revealed its essential roles in these disease conditions, providing potential therapeutic targets for cancer treatment.