Btbd2, a BTB-domain-containing Kelch-like protein, belongs to a small family of proteins specific to animals [1,7]. It has been found to interact with topoisomerase I (TOP1), which is involved in DNA replication and transcription by regulating DNA supercoiling. The interaction between Btbd2 and TOP1 might play a role in various cellular processes related to DNA metabolism [1].

Research shows that Btbd2 localizes to cytoplasmic bodies and co-localizes with TRIM5δ, a RBCC/tripartite motif protein [2]. The polymorphism of Btbd2 rs11670188 is associated with glioblastoma survival, indicating its potential role in this disease [3]. Also, the interaction between Btbd2 and TOP1 requires specific TOP1 residues, and RNAi of Btbd2 in certain cells increases permissiveness to HIV-1 infection, suggesting its involvement in HIV-1 restriction [4]. Additionally, Btbd2, along with BTBD1, forms a complex with E3-RING Cullin 3 ligase, promoting TOP1-cleavage complex ubiquitination and degradation, which is part of the adaptive response to TOP1 inhibitors [5]. It also interacts with HNF1β, enabling TOP1 activation during mitosis and playing a role in chromatin remodeling and gene re-activation after mitosis [6].

In conclusion, Btbd2 is involved in multiple biological processes such as DNA-related activities, sub-cellular localization, and disease-associated functions like glioblastoma survival and HIV-1 restriction. Its interaction with various proteins and its role in different pathways highlight its significance in cellular function and disease mechanisms.