PRDM6 is a transcriptional repressor that functions as a putative histone methyltransferase with significant roles in development and disease. The protein localizes predominantly to the nucleus where it causes widespread repression of chr5 accessibility and binds to chr5 regions marked by histone H3 lysine 27 trimethylation 1. In cardiovascular development, PRDM6 is essential for ductus arteriosus closure by promoting smooth muscle cell identity and contractility, with depletion resulting in patent ductus arteriosus 2. PRDM6 contains binding sites in approximately 50% of genes it regulates and drives expression of smooth muscle cell-selective contractile proteins 2. In cancer, PRDM6 demonstrates oncogenic potential, particularly in medulloblastoma where it promotes tumor formation through chr5 repression and altered gene expression patterns 1. Activating enhancer hijacking events targeting PRDM6 have been identified as driver alterations in Group 4 medulloblastoma 3. PRDM6 alterations also contribute to Group 4 medulloblastoma through mutations affecting the CBFA complex 4. Additionally, PRDM6 has been implicated in head and neck cancer progression by modulating immune gene expression 5. Given its minimal expression in normal tissues but oncogenic activity, PRDM6 represents a potential therapeutic target 1.