In this review, we will discuss recent findings on the significance of APE2 in the context of cancer including synthetic lethality of APE2 in HR-deficient cells (10,25,26), APE2 overexpression trends in cancer types (27), APE2’s role in ATR-Chk1 DDR (16,18), and the newly proposed role of APE2 in the highly mutagenic microhomology mediated end joining (MMEJ) (26). The gene discussed is ATR; the disease is cancer.