FOXN3, also known as CHES1, belongs to the forkhead box (FOX) protein family and acts as a transcriptional inhibitor. It is involved in cell cycle regulation, tumorigenesis, and metabolism [2,3]. It participates in the NF-κB, Smad, and AKT/MDM2/p53 signaling pathways, influencing processes like inflammation, fibrosis, and cell growth [1,5,6]. Genetic models such as transgenic and knockout zebrafish, and mouse models have been crucial for studying its functions [3,6].

In the context of lung inflammation, p38-mediated phosphorylation of FOXN3 at S83 and S85 residues promotes NF-κB activation, as phosphorylated FOXN3 dissociates from hnRNPU, leading to β-TrCP-mediated IκBα degradation. Genetic ablation of FOXN3 phosphorylation confers resistance to MRSA-induced pulmonary inflammatory injury [1]. In ovarian cancer, overexpression of FOXN3 inhibits cell proliferation, migration, invasion, and angiogenesis by negatively regulating RPS15A [4]. In glioma, FOXN3 inhibits cell growth and invasion through inactivating the AKT/MDM2/p53 signaling pathway [6]. In the liver, knockdown of Foxn3 expression decreases fasting glucose and modulates gluconeogenic substrate selection [3].

In summary, FOXN3 plays essential roles in inflammation, tumorigenesis, and glucose metabolism. Model-based research, especially gene knockout studies, has revealed its significant contributions to these biological processes and disease conditions, such as pulmonary inflammatory injury, ovarian cancer, glioma, and glucose regulation.