HELB (DNA helicase B) is a 5'-3' DNA helicase that plays critical regulatory roles in DNA replication initiation and DNA damage response 1. The protein functions as a monomeric, processive motor that translocates along single-stranded DNA (ssDNA) with ATPase activity, binding tightly to ssDNA with a site size of ~20 nucleotides 2. HELB's primary mechanism involves inhibiting DNA end resection by blocking nucleases such as EXO1, BLM, and DNA2 through its ssDNA translocase activity 1. The protein specifically binds to Replication Protein A (RPA) and can clear RPA from ssDNA filaments during translocation, allowing other proteins access to DNA intermediates 2. HELB undergoes cell cycle-dependent regulation, being predominantly nuclear in G1 phase where it participates in replication initiation through interactions with TOPBP1 and CDC45, then relocating to the cytosol after CDK2 phosphorylation at the G1-S transition 1. Disease relevance includes associations with epithelial ovarian cancer susceptibility, particularly non-mucinous subtypes 3, and age at natural menopause through effects on meiotic DNA repair 4. A rare SNP (rs75770066) causing D506G substitution impairs RPA interaction and cellular function, potentially affecting gamete viability 4.