ZBTB25 is a zinc finger and BTB domain-containing transcription repressor that plays multifaceted roles in immune regulation and viral control. Primarily, ZBTB25 functions as a negative regulator of nuclear factor of activated T cells (NF-AT), acting as a T cell-enriched transcription factor that suppresses target gene activation 1. Beyond its transcriptional repression function, ZBTB25 exhibits E3 ubiquitin ligase activity, facilitating proteasomal degradation of viral proteins including coronavirus main protease (Mpro) and influenza viral RNA polymerase 23. Mechanistically, ZBTB25 associates with the HDAC1-Sin3a histone deacetylase complex to repress IL-12B expression in macrophages infected with Mycobacterium tuberculosis, suppressing pro-inflammatory cytokine production 4. In influenza infection, ZBTB25 additionally functions as a viral RNA-binding protein, enhancing viral RNA synthesis through dual mechanisms while simultaneously suppressing interferon production 3. Clinically, ZBTB25 emerges as a biomarker in rheumatoid arthritis pathogenesis, with elevated expression correlating to disease state (AUC=0.911) 5. Its inhibition promotes autophagy-mediated pathogen clearance and represents a therapeutic target for host-directed therapy against tuberculosis and viral infections 42.