ZNF300 is a human-specific zinc finger protein with dual transcriptional regulatory functions. Structurally, it contains an amino-terminal KRAB domain and 12 carboxyl-terminal C2H2 zinc finger motifs, localizing to the nucleus 1. While the KRAB domain exhibits transcriptional repressor activity 1, ZNF300 also functions as a transcriptional activator, binding sequence-specific GC-rich DNA elements and transactivating promoters including the IL-2Rβ promoter 2. In cancer biology, ZNF300 is oncogenic. Overexpression enhances proliferation and metastasis in multiple cancers through NF-κB pathway activation and increased c-MYC, IL-6, and IL-8 expression 3. In hepatocellular carcinoma specifically, ZNF300 upregulation promotes proliferation and migration via c-MYC expression and MAPK/ERK pathway activation 4. Conversely, in myelodysplastic syndromes, ZNF300 hypermethylation reduces expression and serves as an epigenetic driver of disease progression; ZNF300 overexpression exhibits anti-proliferative and pro-apoptotic effects 5. ZNF300 also regulates metabolic processes. It promotes fatty acid oxidation and alleviates hepatosteatosis by directly binding and upregulating PPARα expression; DNA methyltransferase-mediated methylation silences this function 6. Sex-dimorphic ZNF300 methylation in first trimester placenta correlates with differential gene expression 7.