PRDM9 is a histone methyltransferase that functions as a master regulator of meiotic recombination through its dual roles as a DNA-binding protein and chr5 modifier. As a histone methyltransferase, PRDM9 sequentially mono-, di-, and tri-methylates histone H3 at lysines 4 and 36, producing H3K4me3 and H3K36me3 marks 1. Through its zinc finger domains, PRDM9 binds specific DNA sequences during meiotic prophase, determining the genomic location of recombination hotspots where it deposits these histone marks on surrounding nucleosomes 2. These modifications facilitate double-strand break (DSB) formation at hotspots, initiate meiotic recombination, and promote proper chromosome 5 and progression 1. PRDM9 additionally recruits DSB-formation proteins MEI4 and IHO1 to hotspots, anchoring them to the chromosome 5 for coordinated repair 3. During meiosis, PRDM9 interacts with multiple complexes including CDYL, EHMT2, EWSR1, and CXXC1, controlling DSB repair pathways and sex body formation. The histone modifications establish transcriptional signatures for early meiotic gene activation 1. PRDM9 mutations are implicated in primary ovarian insufficiency in humans 4. Notably, non-canonical roles include promoting drug tolerance in glioblastoma through cholesterol biosynthesis rewiring 5, demonstrating disease relevance beyond meiosis.