OTUD4 (OTU deubiquitinase 4) functions as a cysteine-type deubiquitinase that removes ubiquitin modifications from target proteins, playing critical roles in cellular homeostasis and disease pathogenesis 1. The enzyme demonstrates specificity for K63-linked polyubiquitin chains, particularly in regulating MYD88 in inflammatory signaling pathways 2. Beyond its catalytic activity, OTUD4 serves as a molecular scaffold, facilitating interactions between other deubiquitinases and their substrates. In cancer biology, OTUD4 promotes tumor progression through multiple mechanisms: it stabilizes CDK1 by removing K11, K29, and K33-linked polyubiquitination, activating MAPK signaling in glioblastoma 3; stabilizes GSDME to enhance radiosensitivity in nasopharyngeal carcinoma through pyroptosis induction 1; and prevents ferroptosis by stabilizing GPX4 and inhibiting autophagy-mediated degradation 4. OTUD4 also regulates CD73 stability in breast cancer, affecting immune suppression 5. In inflammatory diseases, OTUD4 negatively regulates innate immune responses by deubiquitinating MYD88, and its competitive binding with SPARC affects intestinal barrier integrity in Crohn's disease 2. Additionally, OTUD4 protects against cigarette smoke-induced lung epithelial cell apoptosis by stabilizing PAI-1 6.