PRIMPOL is a dual-function primase and DNA polymerase that initiates de novo DNA synthesis and tolerates replication-stalling lesions by repriming downstream of DNA damage. Acting as an error-prone polymerase, PRIMPOL can synthesize primers past UV lesions, R-loops, and G-quadruplexes to allow replication fork progression 12, and can incorporate nucleotides opposite lesions such as 8-oxoG 3. PRIMPOL repriming leaves behind single-stranded DNA gaps that are subsequently filled by translesion synthesis polymerases including REV1 and POLζ 4. The enzyme functions in both nuclear and mitochondrial DNA replication, being required to reinitiate synthesis after UV damage and chain-terminating lesions 5. In cancer contexts, PRIMPOL expression increases in response to chemotherapeutics, with ATR-dependent phosphorylation regulating its activity 67. BRCA2 suppresses PRIMPOL-mediated repriming through association with MCM10, preventing excessive gap formation 8. PRIMPOL dysfunction is associated with various disorders including dystonia, optic atrophy, and Parkinson disease, and emerging evidence suggests targeting the PRIMPOL pathway may enhance chemotherapy sensitivity in cancer cells, particularly those deficient in BRCA proteins 9.