SUB1 (SUB1 regulator of transcription) is a multifunctional transcriptional coactivator that functions cooperatively with TAFs to mediate interactions between upstream activators and the general transcriptional machinery 1. SUB1 operates throughout the transcription cycle, influencing preinitiation, initiation, elongation, and termination, with direct interaction to the RNA polymerase II stalk domain enabling its pleiotropic effects 2. Beyond transcription, SUB1 binds single-stranded and double-stranded DNA and participates in genome stability maintenance, including binding G-quadruplex DNA structures 1. In inflammatory contexts, SUB1 functions as a master regulator of macrophage TLR2/TLR4 responses, promoting pro-inflammatory M1 polarization through CK2-dependent activation of interferon regulatory factor 1 (Irf1) transcription, thereby enhancing atherosclerotic burden 3. In T cells, SUB1 is induced by TCR-IRF4 signaling and undergoes liquid-liquid phase separation to form biomolecular condensates that drive pathogenic CD4+ T cell migration by trans-activating DOCK2 and partnering with JUNB, establishing SUB1 as a critical gatekeeper of autoimmune T cell trafficking 4. Clinically, elevated SUB1 expression correlates with poor outcomes in colorectal cancer, where it activates NF-κB signaling via UBR5-mediated UBXN1 ubiquitination to promote metastasis 5. These findings position SUB1 as a tractable therapeutic target in inflammatory and malignant diseases.