Jdp2, also known as Jun dimerization protein 2, is a transcriptional modulator involved in multiple biological processes. It participates in pathways related to redox homeostasis, such as the AhR-Nrf2 gene battery where it activates the AhR promoter in a spatiotemporal manner, and is also associated with chromatin remodeling and histone acetylation regulation [2,3,5]. It has significance in various physiological and pathological conditions, including heart-related diseases, cellular senescence, and cancer [1,5,8]. Genetically modified mouse models have been crucial in studying its functions.

In mouse models, overexpression of Jdp2 in the heart leads to cardiac dysfunction, accompanied by hypertrophy and fibrosis, suggesting it contributes to heart failure development [6]. Jdp2-knockout (KO) mice showed that loss of Jdp2 in granule cell progenitors of the cerebellum makes them more resistant to ROS-mediated apoptosis through activation of xCT/Slc7a11 [7]. In the context of acute myeloid leukemia (AML), IRF2BP2 counteracts the ATF7/JDP2 AP-1 heterodimer, and loss of IRF2BP2 leads to over-activation of inflammatory pathways in AML cells [4]. Also, in cancer cells, Jdp2 knockdown enhances sensitivity to TNF-related apoptosis-inducing ligand (TRAIL), indicating it functions as a negative feedback regulator of the ATF4 pathway and contributes to TRAIL resistance [8].

In conclusion, Jdp2 is a key transcriptional modulator involved in diverse biological processes. Mouse models, especially KO models, have revealed its role in heart failure, cerebellum development, and cancer-related processes like apoptosis and inflammatory regulation in AML cells. Understanding Jdp2 provides insights into the mechanisms of these diseases, potentially guiding the development of new therapeutic strategies.