ZHX1 is a nuclear transcription repressor protein containing two zinc fingers and five homeodomain motifs 1. It functions primarily by interacting with transcription factor NF-YA and DNA methyltransferase DNMT3B to suppress gene expression 12. Mechanistically, ZHX1 requires dimerization through its homeodomain for full repressor activity, with an acidic C-terminal region (amino acids 831-873) serving as the repressor domain 3. SUMOylation by Ubc9 at lysine residues 159, 454, and 626 regulates ZHX1 stability and transcriptional activity 4. IL-2 signaling increases ZHX1 mRNA stability through JAK3/STAT5 and PI3K pathways 5. Clinically, ZHX1 dysregulation associates with multiple malignancies. Low ZHX1 expression correlates with hepatocellular carcinoma progression 2, while ZHX1 overexpression promotes proliferation, migration, and invasion in cholangiocarcinoma and glioblastoma, with elevated expression predicting poor survival 67. In minimal change nephrotic syndrome, ZHX1 redistribution to the nucleus during cytokine storms upregulates ANGPTL4, causing proteinuria and podocyte injury 8. These findings suggest ZHX1 as both a prognostic marker and therapeutic target across multiple disease contexts.