SPIDR (scaffold protein involved in DNA repair) functions as a critical scaffolding protein in homologous recombination (HR) repair of DNA double-strand breaks 1. The protein forms part of the human Shu complex, consisting of SWS1, SWSAP1, SPIDR and PDS5B, which promotes RAD51 recruitment to DNA repair foci and facilitates replication fork restart following stalling 1. SPIDR works by enhancing RAD51 filament stability and enabling strand exchange, while also modulating RPA dynamics on single-strand DNA to support high-fidelity DNA repair 2. The protein contains an OB-fold domain, which has been experimentally validated 3. Functionally, SPIDR is essential for maintaining genomic integrity during DNA damage responses and cellular stress conditions 1. Clinically, SPIDR mutations are associated with primary ovarian insufficiency (POI) and ovarian dysgenesis. A homozygous stop-gain mutation (c.839G>A, p.W280*) causes defective homologous recombination, leading to accumulation of DNA double-strand breaks and resulting in gonadal dysgenesis 4. Multiple studies have identified SPIDR variants in POI patients, establishing it as a causative gene for this condition 567. This underscores SPIDR's crucial role in ovarian function and female fertility.