USP13 is a deubiquitinating enzyme that plays crucial roles in multiple cellular processes including autophagy regulation, cell cycle progression, and tumor development. As a deubiquitinase, USP13 stabilizes key regulatory proteins by removing ubiquitin chains, thereby preventing their proteasomal degradation 12. USP13 promotes autophagy by deubiquitinating BECN1 and stabilizing PIK3C3/VPS34-containing complexes, forming regulatory loops that control autophagy and p53 levels 34. The enzyme demonstrates oncogenic properties across multiple cancer types, including lung squamous cell carcinoma where it drives lineage plasticity in club cells and promotes squamous carcinoma development 5. In renal cell carcinoma, USP13 deubiquitinates and stabilizes ZHX2, contributing to tumorigenesis 1. USP13 also regulates immune responses by deubiquitinating STAT1, enhancing chemokine production and CD8+ T cell infiltration 67. Additionally, USP13 mediates a switch between ferroptosis and autophagy through the NFE2L2/NRF2-SQSTM1/p62-KEAP1 axis in KRAS-mutant lung adenocarcinoma 8. The enzyme's diverse substrate specificity and involvement in cancer progression, autophagy, and immune regulation position USP13 as a potential therapeutic target for various diseases, particularly cancers with dysregulated ubiquitination pathways.