OTUD7B is a cysteine-type deubiquitinase that regulates multiple signaling pathways through removal of K48-, K63-, and K11-linked polyubiquitin chains 1. Functionally, OTUD7B acts as a negative regulator of non-canonical NF-κB signaling by deubiquitinating TRAF3, thereby suppressing B-cell activation 2. In T cells, OTUD7B deubiquitinates ZAP70 to modulate TCR signaling and promote normal T cell homeostasis 3. A critical physiological role involves regulating mTOR complex assembly: OTUD7B removes K63-linked ubiquitin chains from MLST8 (GβL) to promote mTORC2 formation and suppress mTORC1, with loss of OTUD7B suppressing Kras-driven lung tumorigenesis 4. In dendritic cells, OTUD7B stabilizes TRAF2 by counteracting K48-ubiquitination, preventing TNF-induced apoptosis and enabling CD8+ T cell priming 5. Recently identified substrate p53 is stabilized by OTUD7B-mediated deubiquitination, exhibiting tumor-suppressive functions in hepatocellular carcinoma 6. OTUD7B also stabilizes β-catenin in non-alcoholic fatty liver disease and HIF-1α in esophageal squamous cell carcinoma 78. In prostate cancer, OTUD7B knockdown inhibits proliferation via AKT/mTOR pathway suppression 9. High OTUD7B expression correlates with favorable prognosis in non-small cell lung cancer 10.