Otub2, also known as otubain-2, is a functional cysteine protease in the OTU family with deubiquitinase activity. It is involved in the deubiquitination of many key proteins in different cell signaling pathways, such as the PD-1/PD-L1 axis, Hippo-independent activation of YAP and TAZ, and regulation of PKM2 activity in glycolysis [1,2,3]. Understanding its function through genetic models like knockout (KO) or conditional knockout (CKO) mouse models can help reveal its role in various biological processes and disease conditions.

Genetic deletion of OTUB2 in tumor cells markedly decreases the expression of PD-L1 proteins on the tumor cell surface, increasing tumor cell sensitivity to CD8+ T-cell-mediated cytotoxicity, which reveals its role in tumor evasion via the PD-1/PD-L1 axis [1]. In colorectal cancer, OTUB2-knockout CRC cells exhibit attenuated proliferation, migration, and increased apoptosis, indicating its role in promoting the progression of CRC through modulating aerobic glycolysis [3].

In conclusion, Otub2 plays diverse roles in different biological processes, especially in cancer-related pathways. KO/CKO mouse models have significantly contributed to understanding its function in tumor evasion, cancer metastasis, and cancer metabolic regulation, providing potential therapeutic targets for cancer treatment.