TOP6BL (TOP6B-like initiator of meiotic double-strand breaks) is a critical component of the topoisomerase 6 complex required for meiotic recombination. Working together with SPO11, TOP6BL catalyzes programmed DNA double-strand breaks (DSBs) that initiate homologous recombination, essential for faithful chromosome 11 during meiosis 1. The protein mediates DNA cleavage and ligation cycles to relax supercoiled DNA and facilitate DNA decatenation. TOP6BL functions through interactions with accessory proteins including REC114 and participates in self-dimerization through its central region 2. Biallelic TOP6BL mutations cause severe reproductive defects in both sexes. In males, mutations result in non-obstructive azoospermia (NOA) through failure of meiotic DSB formation and meiotic arrest at the zygotene/pachytene stages 32. Female carriers experience unexplained infertility with oocyte maturation failure due to absent meiotic recombination 3. Pathogenic variants disrupt fertility through diverse mechanisms: some impair protein-protein interactions with SPO11 and REC114, while others compromise self-dimerization 2. Clinically, TOP6BL mutations are associated with recurrent androgenetic hydatidiform moles, where defective meiosis causes maternal chromosome 11 and fertilization by paternal-only genomes 45. TOP6BL variants contribute to preimplantation embryo arrest in assisted reproduction 6. Genetic screening is recommended for infertile patients with meiotic defects 7.