PRIM2 encodes the regulatory subunit of DNA primase, a critical component of the DNA polymerase alpha-primase complex essential for initiating DNA synthesis 1. During S phase, PRIM2 functions within the replisome complex by coordinating with the catalytic subunit PRIM1 to synthesize short RNA primers on both DNA strands 1. The non-catalytic PRIM2 subunit forms two critical interfaces with the CMG replicative helicase, positioning the primase catalytic domain above the lagging-strand template exit channel to enable efficient primer synthesis 1. PRIM2 binds RNA:DNA duplexes and orchestrates the catalytic activities of PRIM1 and POLA2 during the primase-to-polymerase switch 1. Beyond replication, PRIM2 has emerged as a significant oncogenic marker. High PRIM2 expression is associated with poor prognosis in pancreatic ductal adenocarcinoma (PDAC), functioning as an independent survival risk factor 2. PRIM2 promotes PDAC proliferation and metastasis through interactions with FAM111B, modulating PI3K/AKT and epithelial-mesenchymal transition pathways 3. In gliomas, PRIM2 serves as a marker of MYC-driven cell cycle progression and hyper-proliferation, predicting aggressive disease and poor survival 4. Additionally, PRIM2 genetic variants are associated with survival outcomes in non-small cell lung cancer 5, and PRIM2 downregulation induces ferroptosis in lung cancer cells 6.