APOBEC3D is a cytidine deaminase that functions in innate antiviral immunity and contributes to both cancer restriction and progression. As an antiviral factor, APOBEC3D restricts HIV-1 replication by being packaged into viral particles and inducing G-to-A hypermutations in the viral genome 1, with demonstrated anti-HIV-1 activity confirmed in humanized mouse models 2. APOBEC3D also participates in restricting other retroviruses, though it may enhance hepatitis B virus replication through competitive exclusion of other restriction factors from viral capsids. The enzyme catalyzes cytosine-to-uracil deamination in single-stranded DNA and RNA 3, localizing to the cytoplasm and nucleus 4. In cancer contexts, APOBEC3D promotes genomic mutagenesis and therapy resistance: it facilitates pancreatic cancer cell survival under gemcitabine-induced DNA replication stress by enabling replication fork restart and repair 5. Additionally, elevated APOBEC3D expression correlates with poor prognosis and increased somatic mutations in clear cell renal cell carcinoma 6. Beyond its deamination-dependent functions, APOBEC3D interacts with prefoldin chaperone proteins in RNA-independent interactions, suggesting deamination-independent cellular roles 4. These dual functions position APOBEC3D as both a host defense factor and a potential contributor to cancer mutagenesis and chemotherapy resistance.