First-generation PRMT5 inhibitors enteringclinical trials wereeither SAM competitive (JNJ-64619178 and PF-06939999) or SAM uncompetitive(GSK3326595 and EPZ015666) (Figure 1).18−21 However, concerns regarding dose-limiting side effects such as anemia,thrombocytopenia, and neutropenia were apparent.22,23 Consequently, several PRMT5 ligands acting via different mechanisms(e.g., proteolysis targeting chimeras) are being investigated as potentialcancer therapeutics.12 The gene discussed is PRMT5; the disease is neutropenia.