SP110 is a nuclear transcription factor and coactivator of nuclear hormone receptors 1 that regulates genes containing retinoic acid response elements. SP110 functions as a positive regulator of inflammatory and interferon response genes during pathogen infection. In Mycobacterium tuberculosis-infected macrophages, SP110 acts as a positive regulator of type I interferon response genes and inflammatory gene expression; depletion of SP110 impairs induction of these genes 2. Similarly, SP110 is required for Anaplasma phagocytophilum infection establishment, with Sp110 mRNA levels increasing during infection and RNA interference knockdown reducing bacterial infection levels 1. During hepatitis B virus infection, SP110 undergoes ubiquitination by UBR7 E3 ligase at its SAND domain, which downregulates type I interferon response pathway genes, promoting viral persistence and hepatocellular carcinoma development 3. Regarding tuberculosis susceptibility, genetic studies show conflicting results. While SP110 SNP rs9061 showed significant association with TB risk in meta-analyses 45, other studies found no significant associations in specific populations 67, and an earlier meta-analysis concluded no robust evidence for SP110 involvement in TB susceptibility 8. SP110 mutations are associated with hepatic venoocclusive disease with immunodeficiency, reflecting its critical role in immune regulation.