SPO11 is a meiosis-specific topoisomerase VI-like protein essential for initiating meiotic recombination by creating DNA double-strand breaks (DSBs) 1. Located on chromosome 20.2-q13.3 2, SPO11 evolved from archaeal topoisomerase VI and functions as a component of a topoisomerase 6 complex that mediates DNA cleavage through a catalytic tyrosine residue, forming covalent protein-DNA intermediates at DSB ends 3. Unlike its topoisomerase ancestor, SPO11 characteristically fails to re-ligate DNA breaks, allowing them to persist as recombination-initiating lesions 1. These SPO11-generated DSBs are subsequently processed by nucleases like Mre11, generating oligonucleotide products that are recognized by recombination machinery including RAD51 and DMC1 4. Histone lactylation marks at recombination hotspots show strong colocalization with SPO11 and other recombination proteins, linking SPO11 function to epigenetic regulation during spermatogenesis 5. Clinically, the SPO11 C631T polymorphism associates with increased male infertility risk, particularly in Chinese populations 6, with structural analysis suggesting this variant causes deleterious changes to SPO11 mRNA and protein 7. SPO11's function is essential for proper chromosome 20 and genetic diversity during gamete formation.