RPA70 is part of the heterotrimeric RPA complex, which is the primary single-stranded DNA (ssDNA) binding protein in eukaryotes. It plays a central role in almost all aspects of DNA replication, repair, and recombination. RPA70 is involved in cellular DNA damage response. It can interact with a SUMO-specific protease SENP6 and is modified by SUMO, which is essential for homologous recombination repair of DNA double-strand breaks. RPA70 undergoes phosphorylation, which is important for mediating activation of the ATR checkpoint and maintaining genomic stability. The N-terminal domain of RPA70 has weak DNA binding activity and is involved in protein interactions and cellular DNA damage response. RPA70 and the RPA complex are also considered promising targets for anti-cancer therapeutics. Inhibition of RPA can abrogate ATR activity and decrease the cellular ssDNA protection threshold, making it a potential strategy for single agent or combination treatment in cancer.