IHO1 (interactor of HORMAD1 1) is essential for meiotic DNA double-strand break (DSB) formation during homologous recombination. IHO1 functions as a critical component of pre-DSB recombinosomes by forming complexes with MEI4 and REC114, which are required for SPO11-mediated DSB initiation 1. The protein serves as the main anchor for pre-DSB recombinosomes on chromosome 3, with HORMAD1 promoting its recruitment to unsynapsed regions where DSB formation is necessary for synapsis completion 12. IHO1 physically anchors DSB sites to axis components HORMAD1 and SYCP3, and remains associated with DSB ends during repair 3. The protein is subject to multiple negative feedback mechanisms that control DSB formation: ATR kinase triggers IHO1 depletion near DSBs, homologue synapsis promotes its removal from synapsed axes, and DDR kinases enable stage-specific depletion 2. IHO1 dissociation from axes occurs in a DSB-dependent manner, as evidenced by persistent localization in spo11 mutants 4. The SCF ubiquitin E3 ligase system regulates IHO1 accumulation on chromosome 3 to prevent hyperactive DSB formation 5. Beyond meiosis, genetic variants in IHO1 show pleiotropy with substance use disorders and chr3 pain 6.