Brd4, a member of the Bromodomain and Extraterminal (BET) protein family, is an epigenetic reader that binds to acetylated histone marks. It plays pleiotropic roles in regulating gene transcription, especially in the organization of super-enhancers (SEs) and the expression of oncogenes. Additionally, Brd4 is involved in maintaining genome stability, controlling DNA damage checkpoint activation, repair, and telomere maintenance [1]. It also participates in multiple cellular processes relevant to various diseases, such as cell proliferation, apoptosis, and different forms of programmed cell death [7].

In cancer, inhibition of Brd4 can disrupt the communication between SEs and target promoters, leading to cell-specific repression of oncogenes and subsequent cell death [1]. For example, in glioblastoma, several Brd4 inhibitors and degraders have shown promise in suppressing the disease, though the exact role and mechanism in its pathogenesis are yet to be fully elucidated [2]. In NUT carcinoma, the BRD4-NUT fusion oncoprotein drives the disease, potentially acting through the formation of massive super-enhancers [4]. In acute gouty arthritis, targeting Brd4 can prevent the disease by regulating pyroptosis [3]. Also, Brd4 is involved in the life-cycle of human papillomaviruses and is a potential target for associated cancers [5]. In lung diseases, Brd4 has been identified as a potential therapeutic target [6].

In conclusion, Brd4 is a crucial protein involved in gene transcription regulation and genome stability maintenance. Its role in various diseases, especially cancer, has been well-studied through in vivo and in vitro experiments. Research on Brd4, including gene knockout (KO) or conditional knockout (CKO) mouse models, has provided insights into its functions in specific biological processes and disease conditions, highlighting its potential as a therapeutic target.