Kdm5a, also named RBP2 or JARID1A, is a lysine-specific demethylase that can remove methyl groups from histones H3K4me1/2/3. Histone methylation is a key post-translational chromatin modification, and Kdm5a, as a member of the KDM5 Jumonji histone demethylase subfamily, is involved in multiple cellular processes such as differentiation, metabolism, cell cycle, and transcription [1,2,3]. It is also associated with various diseases, especially cancers [1,2].

In cancer, Kdm5a is aberrantly expressed. Pharmacological inhibition of Kdm5a significantly attenuates tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia, indicating its potential as a drug target in cancer therapy [1]. In HIV-1 latent infection, Kdm5A/B function as host repressors of HIV-1 lytic reactivation, promoting latency and the survival of infected reservoirs [4]. In replication stress response, Kdm5A, together with Kdm5B, contributes to the response and tolerance by regulating RRM2 and the activation of Chk1 [5]. In lung adenocarcinoma, Kdm5A is up-regulated and regulates cell proliferation and gefitinib drug resistance [7]. In pediatric leukemia, the NUP98-KDM5A chimeric protein generates genomic instability, likely contributing to malignant transformation [6].

In conclusion, Kdm5a is an important epigenetic regulator involved in multiple biological processes and disease conditions. Its role in cancer, HIV-1 latent infection, replication stress response, and other diseases has been revealed through various studies. Understanding the function of Kdm5a provides potential targets for disease treatment, especially in cancer therapy.