OTUD1 (OTU deubiquitinase 1) is a deubiquitinating enzyme that specifically hydrolyzes K63-linked polyubiquitin chains to regulate multiple cellular pathways 1. The protein functions as a critical regulator of inflammatory responses by suppressing NF-κB signaling through deubiquitination of key signaling factors including LUBAC and RIPK1 12. OTUD1 also modulates oxidative stress responses by binding KEAP1 via its N-terminal ETGE motif and regulating NRF2 stability, thereby controlling antioxidant pathways and ROS-associated cell death 13. In cardiac physiology, OTUD1 plays context-dependent roles: it drives diabetic cardiomyopathy by deubiquitinating AMPKα2 and impairing mitochondrial function 4, while also promoting inflammatory heart remodeling through macrophage CARD9 activation 5. The enzyme exhibits tumor suppressor activities by enhancing iron transport through IREB2 stabilization, promoting ferroptosis and antitumor immunity 6. However, OTUD1 can also form cytoplasmic aggresomes that activate ASK1/JNK signaling to maintain cancer stem cell properties in ovarian cancer 7. Clinical relevance is demonstrated by OTUD1's protective role against inflammatory bowel disease and its association with cancer prognosis 26.