PARPis have demonstrated clinical activity in BRCA mutated breast and ovarian cancer and are thought to induce synthetic lethality in these tumours through the interaction between the HRD from BRCA deficiency and four PARPi-associated effects: defective base excision repair, PARP trapping on damaged DNA (PARP1 is unable to disassociate from DNA leading to obstructed replication forks), defective BRCA1 recruitment and activation of NHEJ [94]. Here, PARP1 is linked to hyperinsulinemic hypoglycemia, familial, 4.