HMGN4 (high mobility group nucleosomal binding domain 4) is a nucleosome-binding protein encoded by an intronless gene at chromosome 6.3 1 that regulates chr6 organization and gene expression. As a non-histone chr6-associated protein, HMGN4 localizes to the nucleus where it interacts with nucleosomes and histone proteins, particularly Hist1H1A and Hist1H3A 2. HMGN4 alters cellular transcription profiles; elevated expression downregulates tumor suppressors (Atm, Atrx, Brca2) and increases DNA damage markers, thereby potentiating thyroid tumorigenesis 3. HMGN4 also facilitates nuclear translocation of the transcription factor IRX5, promoting de novo fatty acid synthesis and HCC development 4. Clinically, HMGN4 is upregulated across multiple malignancies including thyroid cancer, gastric cancer, and hepatocellular carcinoma (HCC) 35. Elevated HMGN4 expression correlates with poor prognostic outcomes in HCC, including high-grade tumors and shorter overall survival 6, and participates in immune infiltration patterns associated with fibrotic progression to HCC 7. Its involvement in crotonylation-mediated pathways further links HMGN4 to HCC prognosis and drug sensitivity 8, establishing it as a potential diagnostic and therapeutic target.