USP33 is a deubiquitinating enzyme that regulates diverse cellular processes through substrate-specific deubiquitination. The enzyme removes K48- and K63-linked ubiquitin chains from multiple target proteins, leading to their stabilization 1. USP33 plays critical roles in mitochondrial quality control by deubiquitinating PRKN/parkin, thereby antagonizing mitophagy and affecting neuronal cell survival 1. In cancer contexts, USP33 demonstrates dual roles: it promotes ovarian cancer progression by stabilizing CBX2 through K27- and K48-linked deubiquitination 2 and facilitates esophageal squamous cell carcinoma metastasis by deubiquitinating integrin α6 3. Conversely, USP33 exhibits tumor-suppressive functions in triple-negative breast cancer by stabilizing TAP63 via K48-linked deubiquitination, activating autophagy and ferroptosis pathways 4. The enzyme also functions as a p53 deubiquitinase, stabilizing p53 under DNA damage conditions and regulating DNA damage responses 5. Additionally, USP33 modulates ferroptosis in endometriosis by repressing the Hippo-YAP pathway through LATS1 deubiquitination 6. In viral infections, USP33 promotes SARS-CoV-2 replication by stabilizing the viral envelope protein 7. These findings highlight USP33's context-dependent functions in cellular homeostasis, cancer biology, and infectious disease.