PBLD (phenazine biosynthesis-like domain-containing protein) functions as a positive regulator of antiviral innate immunity and tumor suppression. In antiviral responses, PBLD enhances type I interferon (IFN-I) production through multiple pathways: it activates NF-κB signaling by inhibiting TRIM21-mediated degradation of phosphorylated IKKβ 1, promotes the p53-USP4-MAVS signaling axis by stabilizing MAVS through USP4-mediated deubiquitination 2, and modulates STING-dependent antiviral responses by suppressing CCDC50-mediated selective autophagic degradation of STING 3. PBLD-deficient mice show increased susceptibility to viral infections compared to wild-type littermates 23. As a tumor suppressor, PBLD is frequently downregulated in hepatocellular carcinoma, with decreased expression correlating with poor prognosis, advanced tumor stage, and reduced survival 4. PBLD inhibits cancer cell growth and invasion by inactivating MAPK, NF-κB, EMT, and angiogenesis signaling pathways 4. Additionally, PBLD contributes to intestinal barrier repair in ulcerative colitis through the mTOR/PBLD/AMOT pathway 5 and plays roles in macrophage polarization via VDR-dependent mechanisms 6. Clinically, PBLD expression is elevated in autoimmune diseases like systemic lupus erythematosus 3.