HELQ encodes a highly conserved 3'-5' DNA helicase that plays crucial roles in maintaining genome stability through multiple DNA repair pathways 1. The protein functions primarily in homology-driven double-strand break (DSB) repair mechanisms, including homologous recombination, single-strand annealing, microhomology-mediated end-joining, and synthesis-dependent strand annealing 1. HELQ possesses dual biochemical activities: DNA unwinding and strand annealing capabilities 2. The helicase regulates DNA end resection at DSBs, promoting EXO1-mediated resection through its helicase activity, while also protecting stalled replication forks from degradation via its ssDNA-binding capacity 3. HELQ interacts functionally with multiple proteins including RAD51, RPA, DNA polymerase delta, and XRN2 exoribonuclease, with the latter interaction facilitating R-loop resolution 42. Clinically, HELQ deficiency is associated with primary ovarian insufficiency and subfertility due to its critical role in germ cell stability and proper cell-fate transitions during male germ cell development 56. Additionally, abnormal HELQ expression has been observed in multiple tumors, suggesting its involvement in tumorigenesis 78.