RPA2 is the 32 kDa subunit of the heterotrimeric replication protein A complex, functioning as a master regulator of single-stranded DNA metabolism. As part of RPA, RPA2 binds and stabilizes ssDNA intermediates during DNA replication and DNA damage responses, preventing reannealing while recruiting repair proteins including RAD51, RAD52, XPA, and XPG 1. RPA2 activates ATR kinase through ATRIP recruitment and participates in nucleotide excision repair, base excision repair, and homologous recombination pathways 1. During replication stress, phosphorylated RPA2 (pRPA2-S33) localizes to DNA damage sites and activates CHK1 checkpoint signaling 2. RPA2 also maintains telomere stability; variants impairing RFWD3 ubiquitination cause premature telomere shortening and telomere biology disorders 3. Clinically, elevated phospho-RPA2-T21 foci predict platinum and PARP inhibitor sensitivity in homologous recombination-proficient ovarian cancers, serving as a replication stress biomarker 4. RPA2 abundance correlates with DNA repair efficiency; elevated RPA2 enhances double-strand break repair fidelity 5. Additionally, RPA2 suppresses disease-associated CAG repeat expansions in Huntington disease and spinocerebellar ataxia, while alternative-RPA antagonistically promotes expansions 1. RPA2's N-terminal phosphorylation is conserved across species and critical for damage checkpoint control 6.