Since RB1 loss-of-function alterations confer resistance to CDK4/6i in ER+ metastatic breast cancer patients [91,92], a genome-wide CRISPR screen identified protein arginine methyltransferase 5 (PRMT5) as a vulnerability in ER+/RB1-deficient breast cancer cells [93]. The gene discussed is CDK4; the disease is breast carcinoma.