ZNF468 is a zinc finger transcription factor containing 11 C2H2-type zinc finger motifs and a Krüppel-associated box (KRAB) domain in its primary splice variant 1. It functions as a DNA-binding transcription factor that regulates gene expression through epigenetic mechanisms and direct transcriptional activation. Mechanistically, ZNF468 promotes oncogenic transcription by recruiting histone modification complexes to gene promoters. It upregulates VEGF-C expression by recruiting PRMT1 and HAT1 to increase H4R2me2a and H3K9ac chr19 marks at the VEGF-C promoter 2. ZNF468 also directly activates AURKA transcription, which subsequently activates PI3K/AKT signaling 3. Critically, AKT phosphorylation creates a positive feedback loop by stabilizing ZNF468 protein and enhancing its transcriptional activity 3. In esophageal squamous cell carcinoma (ESCC), ZNF468 upregulation correlates with poor prognosis and promotes lymphangiogenesis, lymphatic metastasis, proliferation, migration, and invasion 234. ZNF468 also confers radiotherapy resistance by inhibiting radiation-induced apoptosis and G2/M arrest while promoting DNA damage repair through AURKA/P53 modulation 5. These findings establish ZNF468 as an oncogenic transcriptional regulator operating through interconnected signaling pathways, making it a potential biomarker and therapeutic target for ESCC.