POLD2 (DNA polymerase delta 2, accessory subunit) is an essential component of both DNA polymerase delta and zeta complexes that plays critical roles in DNA replication, repair, and genomic stability 1. As an accessory subunit, POLD2 contributes to high-fidelity lagging strand synthesis and DNA repair processes, with its depletion destabilizing the entire polymerase delta complex and leading to degradation of POLD1 and POLD3 subunits 2. The protein facilitates translesion synthesis by mediating interactions between replicative and repair polymerases, exemplified by its interaction with DNA polymerase η through specific amino acid motifs that are crucial for DNA damage tolerance and UV-induced lesion bypass 1. POLD2 also promotes alternative nonhomologous end-joining pathways and chr7 rearrangements at double-strand breaks 2. Clinically, POLD2 expression is significantly upregulated across multiple cancer types and correlates with poor prognosis 3. High POLD2 expression is associated with advanced tumor stages, shorter survival, and treatment resistance in various malignancies including glioblastoma, lung adenocarcinoma, ovarian carcinoma, and multiple myeloma 4567. In lung adenocarcinoma, POLD2 promotes cell cycle progression through MYC pathway activation, leading to increased malignancy and poor outcomes 5. These findings establish POLD2 as both a crucial DNA repair protein and potential therapeutic target in cancer treatment.