Foxo4, a member of the FOXO family, is a transcription factor that regulates genes involved in metabolism, cell cycle, apoptosis, and cellular homeostasis. It also mediates cell responses to oxidative stress and antitumor agents, and is linked to the progression of several diseases [3]. Its activity is regulated by post-translational modifications and interaction with other proteins.

In renal ischemia/reperfusion injury, inhibition of Brd4 blocked renal apoptotic and ERS protein expression by preventing FoxO4-dependent ROS generation through the PI3K/AKT pathway [1]. In vascular smooth muscle cells, XBP1u interacted with FoxO4's N-terminus, preventing its nuclear translocation and thus maintaining the contractile phenotype and protecting from aortic aneurysm formation [2]. In hemochorial placentation, disruption of FoxO4 in a genome-edited rat model led to placentomegaly, indicating its role in regulating placental development [4]. In vascular smooth muscle, FoxO4 knockdown decreased sGCβ expression, cGMP production, and downstream phosphorylation, showing its role as a transcriptional regulator of sGCβ [5].

In summary, FoxO4 is crucial for multiple biological processes. Model-based research, such as gene knockout in mice and rats, has revealed its significance in diseases like renal ischemia/reperfusion injury, aortic aneurysm, and in placental development. Understanding FoxO4's functions provides insights into disease mechanisms and potential therapeutic targets.