USP22 is a deubiquitinase that regulates multiple cellular processes through stabilization of key proteins. As part of the SAGA complex, USP22 functions as a transcriptional coactivator by deubiquitinating histones H2A and H2B 1. USP22 plays critical roles in immune regulation by stabilizing transcription factor FOXP3 in regulatory T cells, where its loss leads to spontaneous autoimmunity but enhanced anti-tumor immunity 1. In cancer contexts, USP22 promotes tumorigenesis through multiple mechanisms: it stabilizes PD-L1 to enhance immune evasion 2, drives immune checkpoint blockade resistance by stabilizing EZH2 which silences MHC-I expression 3, and promotes cancer stemness and drug resistance in hepatocellular carcinoma through HIF-1α stabilization 4. Additionally, USP22 regulates lipid metabolism by stabilizing PPARγ, contributing to hepatocellular carcinoma development 5, and facilitates breast cancer metastasis by stabilizing FOXO1 in epinephrine-induced lipolysis pathways 6. Conversely, USP22 exhibits anti-inflammatory properties by promoting NLRP3 degradation through ATG5-dependent autophagy 7. These diverse functions make USP22 a promising therapeutic target for cancer immunotherapy and inflammatory diseases.