ZKSCAN4 is a zinc finger transcription factor containing KRAB and SCAN domains located on chromosome 6. It functions as an RNA polymerase II-specific DNA-binding transcription factor involved in regulating gene expression 1. In the hippocampus, ZKSCAN4 promotes stress resilience by directly binding the Htr2a promoter and recruiting glucocorticoid receptors to transcriptionally repress the 5-hydroxytryptamine receptor 2a gene, thereby reducing excitatory synaptic transmission 1. Reduced hippocampal ZKSCAN4 expression is observed in patients with major depressive disorder and stress-susceptible mice; ZKSCAN4 disruption is sufficient to induce depression-like behaviors following subthreshold stress 1. ZKSCAN4 also interacts with phosphorylated YY1 to induce HDM2 gene expression in endothelial cells under disturbed flow conditions, contributing to atherosclerosis development 2. Genetically, ZKSCAN4 variants have been associated with schizophrenia and bipolar disorder 34, and ZKSCAN4 methylation status is associated with myopia risk and responds to environmental temperature exposure 56. Recent studies identified ZKSCAN4 as a potential drug target for lung cancer treatment 7. These findings suggest ZKSCAN4's role in neuropsychiatric resilience, vascular function, and disease susceptibility.