Subsequently, a biomarker-driven Phase II study will randomize patients according to USP activity strata (USP22-high vs. USP3-low) and prioritize combination regimens with complementary pathway inhibition, exemplified by pairing a USP7 inhibitor with a PARP inhibitor for the HRD subtype, thereby closing the precision-medicine loop. The gene discussed is PARP1; the disease is hypoparathyroidism-retardation-dysmorphism syndrome.