BTBD2 (BTB domain containing 2) is a protein-protein interaction mediator that plays important roles in transcriptional regulation, DNA repair, and cellular restriction mechanisms. The protein contains a BTB/POZ domain that facilitates protein-protein interactions 1. BTBD2 functions as a cofactor for the transcription factor HNF1β, enabling the recruitment and activation of Topoisomerase 1 (TOP1) specifically during mitosis to promote DNA relaxation and chr19 remodeling around mitotic binding sites 2. Additionally, BTBD2 interacts with TOP1 through specific residues (236 and 237) that are critical for HIV-1 viral tropism, and RNAi-mediated depletion of BTBD2 increases cellular permissiveness to HIV-1 infection by 2-3 fold 3. The protein localizes to cytoplasmic bodies where it colocalizes with TRIM5δ, which serves as a scaffold for BTBD2 assembly and may involve ubiquitin-mediated processes 4. BTBD2 has clinical relevance as a tumor antigen recognized by HLA-A2402-restricted cytotoxic T lymphocytes in lung cancer 5, and polymorphisms in BTBD2 are associated with glioblastoma survival outcomes through involvement in double-strand break repair pathways 6. The gene is expressed across multiple cancer types and shows decreased expression in multiple myeloma cells treated with arsenic trioxide 7.