HOXB13 is a homeodomain transcription factor that functions as a sequence-specific DNA-binding regulator with critical roles in prostate biology and development. As a transcriptional repressor, HOXB13 preferentially binds methylated DNA 1 and regulates genes involved in cellular identity and differentiation. In prostate tissue, HOXB13 collaborates with FOXA1 to reprogram androgen receptor (AR) binding sites; introduction of both factors into immortalized cells recapitulates the tumor cistrome pattern, mechanistically linking them to prostate epithelial transformation 2. HOXB13 also recruits histone deacetylase HDAC3 to suppress de novo lipogenesis through histone deacetylation at lipogenic enhancers, independently of AR signaling 3. Functionally, HOXB13 maintains FOXA1 binding at the AR enhancer and directly regulates PSMA expression in both AR-positive and AR-negative prostate cancer contexts 4, 5. Clinically, HOXB13 mutations (particularly G84E) are associated with early-onset and hereditary prostate cancer susceptibility 6, 7. Notably, HOXB13 is hypermethylated and downregulated in approximately 30% of metastatic castration-resistant prostate cancer, with loss promoting lipid accumulation and tumor metastasis—a phenotype potentially targetable by fatty acid synthase inhibitors 3. These findings establish HOXB13 as a central epigenetic regulator in prostate tumorigenesis and a candidate biomarker for personalized therapy selection.