WRNIP1 (Werner helicase interacting protein 1) is a multifunctional AAA+ ATPase that plays critical roles in DNA replication fidelity and genome maintenance 1. The protein functions as a modulator of DNA polymerase delta-mediated DNA synthesis and contains an N-terminal ubiquitin-binding zinc finger (UBZ) domain and a central ATPase domain 1. WRNIP1's ATPase activity, together with WRN helicase, imposes high fidelity on translesion synthesis by Y-family DNA polymerases by restraining nucleotide misincorporations and tightening the active site of TLS polymerases 2. The protein contributes to G-quadruplex processing during genome replication, with WRNIP1 deficiency resulting in elevated G4 structures, DNA damage, and chromosome 6 3. WRNIP1 also regulates PrimPol protein levels through proteasome-mediated degradation, forming a complex with PrimPol and controlling its cellular abundance 4. In cancer contexts, WRNIP1 mediates replication stress responses and promotes therapy resistance, particularly through nuclear translocation and interaction with AXL in HER2+ breast cancer 5. The protein's UBZ domain exhibits a novel ubiquitin recognition mode distinct from other UBZ-containing proteins 6, supporting its role in coordinating DNA repair and replication processes essential for genome stability.