APOBEC3A is a cytidine deaminase that catalyzes cytosine-to-uridine editing of single-stranded DNA, particularly in stem-loop secondary structures 1. As part of the innate immune response, APOBEC3A potently restricts viral infections, including human papillomavirus and herpesviruses, by editing viral genomes 23. However, APOBEC3A also generates prevalent mutational signatures in human cancer cells, with evidence establishing it as the primary driver of APOBEC3-associated mutations across breast, bladder, and lymphoma cancers 4. Therapy-induced APOBEC3A expression in lung cancer cells drives sustained mutagenesis and genomic instability in drug-tolerant persisters, promoting evolution toward acquired drug resistance 5. APOBEC3A activity is detected in lung cancer tumors through RNA single-base substitution signatures, linking its expression to intratumoral heterogeneity and metastatic potential 6. The enzyme generates distinct single-strand cytosine deamination damage signatures detectable at single-molecule resolution 7. APOBEC3A is enriched in specific immune cell subsets within ovarian cancer microenvironments 8. This dual functionality—antiviral defense versus cancer-promoting mutagenesis—represents a critical clinical consideration, as APOBEC3A suppression may prevent acquired resistance to targeted therapies.