PRDM5 (PR/SET domain 5) is a sequence-specific DNA-binding transcription factor that functions primarily as a transcriptional repressor 1. It recruits histone methyltransferase EHMT2/G9A and histone deacetylases such as HDAC1 to suppress gene transcription. PRDM5 regulates genes involved in hematopoiesis and extracellular matrix development, including fibrillar collagens (COL4A1, COL11A1), connective tissue components (HAPLN1), and molecules regulating cell migration and adhesion (EDIL3, TGFB2). In cancer cells, PRDM5 induces G2/M arrest and apoptosis, suggesting tumor-suppressive functions 1. PRDM5 is frequently silenced in multiple cancer types through promoter hypermethylation, including breast, ovarian, liver, colorectal, and esophageal cancers 23. Low PRDM5 expression correlates with poor prognosis in esophageal squamous cell carcinoma and associates with reduced overall survival 34. Beyond malignancy, PRDM5 loss-of-function mutations cause brittle cornea syndrome, characterized by corneal thinning, myopia, and blue sclerae, reflecting its role in extracellular matrix integrity 56. Recent evidence implicates PRDM5 variants in aortic and arterial aneurysm diseases 6. In liver tumorigenesis, PRDM5 acts as a microenvironment-dependent lineage commitment factor 7.