PARP inhibition is now a standard of care for treating HRR-defective tumors including advanced prostate cancers with biallelic BRCA2 and PALB2 loss, with this improving OS and quality of life.2,3,7 Elucidating mechanisms of PARPi resistance can guide the development of next-generation therapeutic strategies for these subjects. Here, PALB2 is linked to Familial prostate cancer.