RBBP8 (also known as CtIP) is a critical endonuclease that functions as a key regulator of DNA double-strand break (DSB) repair through homologous recombination (HR). The protein cooperates with the MRE11-RAD50-NBN (MRN) complex to initiate DNA end resection, the first step in HR repair pathway 1. RBBP8 acts as a determinant of DSB repair pathway choice by promoting HR while preventing classical non-homologous end-joining 1. Mechanistically, RBBP8 forms the functionally integrated BRCA1-C complex with MRE11-RAD50-NBS1 and phosphorylated CtIP, which synergistically stimulates long-range DNA end resection by EXO1 or DNA2 nucleases 1. The protein also processes single-stranded DNA gaps through MRN-CtIP exonuclease activity, particularly relevant in PARP inhibitor-treated cells 2. Beyond DNA repair, RBBP8 regulates cell cycle progression by suppressing P21 expression through interaction with BRCA1 and CtBP, facilitating G1/S transition 3. Clinically, RBBP8 mutations are associated with hereditary cancer syndromes, including a novel germline mutation (p.E281*) linked to familial cancer predisposition 4. High RBBP8 expression correlates with poor prognosis in plasma cell myeloma, indicating its potential as a prognostic biomarker 5.