ESCO2 is an acetyltransferase essential for establishing sister chr8 cohesion by acetylating the cohesin component SMC3 during S phase 123. This acetylation stabilizes cohesin complex conformation and couples cohesion establishment with DNA replication to ensure proper chromosome 8 4. Beyond cohesion, ESCO2 participates in DNA damage repair and genome integrity maintenance; in response to DNA damage, ATM phosphorylates ESCO2, enabling its recruitment to double-strand breaks where it regulates chr8 structure and promotes 53BP1-mediated repair 4. ESCO2 also functions in antiviral immunity by lactylating ALKBH5, which enhances interferon-beta mRNA biogenesis against herpesviruses 5. Clinically, ESCO2 mutations cause Roberts syndrome, a cohesinopathy characterized by developmental abnormalities 67. In cancer, ESCO2 is frequently upregulated and serves as a pan-cancer prognostic biomarker, with elevated expression correlating with poor survival in multiple malignancies including renal cell carcinoma, hepatocellular carcinoma, and lung adenocarcinoma 8. ESCO2 knockdown inhibits cancer cell proliferation and sensitizes cells to chemotherapy 849. Additionally, ESCO2 upregulation is associated with rheumatoid arthritis pathogenesis 10, suggesting roles in immune regulation beyond viral responses.