Based on limited published evidence, REXO5 is a nuclear 3'→5' exoribonuclease with exonuclease activity involved in RNA processing. It localizes to the nucleolus and nucleus where it participates in rRNA 3'-end processing and is present in extracellular exosomes. Recent evidence reveals REXO5 promotes genomic integrity by regulating R-loop levels through its exonuclease domain; REXO5 knockout cells accumulate R-loops and show increased DNA damage with ATR-CHK1 pathway activation 1. The enzyme demonstrates selective 3'→5' exoribonuclease activity on single-stranded RNA substrates 2. REXO5 expression is elevated in chr16 myeloid leukemia patients, suggesting involvement in disease pathogenesis.