Brd2, a member of the bromodomain and extra-terminal (BET) family, is a chromatin regulator. It interprets histone Kac modification epigenetic information, controlling gene expression, chromatin structure remodeling, and preventing DNA damages from replicative stress [6]. It is involved in multiple biological processes and disease-related pathways. Genetic models, such as gene knockout (KO) mouse models, are valuable for studying its functions.

In glioblastoma (GBM), phosphocreatine (PCr) produced by GBM stem cells stabilizes Brd2, promoting epigenetic reprogramming and tumor growth. Disrupting PCr biosynthesis leads to Brd2 degradation, inhibiting chromosome segregation and cell proliferation [1]. In B-cell antibody class switch recombination (CSR), Brd2 suppresses alternative end-joining (AEJ) and aberrant recombination, and its deficiency impairs switch region synapse and DNA damage response [2]. In osteoarthritis, the BRD2-specific inhibitor BBC0403 reduces catabolic factors, PGE2 production, and ECM degradation, preventing cartilage degradation by suppressing NF-κB and MAPK signalling pathways [3]. Brd2 haploinsufficiency in C57B6/J mice extends lifespan, increases healthspan, and reduces cancer incidence [4]. In SARS-CoV-2 infection, BRD2 is required for ACE2 transcription, and its inhibitors block virus infection [5]. In cholesterol deprivation, BRD2 cooperates with SREBP2 to regulate sigma-2 receptor (S2R) transcription [7]. In obesity, Brd2 knockdown in mice prevents obesity-induced inflammatory responses and uncouples obesity from diabetes [8].

In conclusion, Brd2 is crucial in diverse biological processes and disease conditions. Model-based research, especially KO mouse models, has revealed its roles in cancer, immune response, aging, viral infection, cholesterol regulation, and metabolic diseases. Understanding Brd2's functions provides potential therapeutic targets for these diseases.