Recent studies have provided significant mechanistic and translational insights into the regulation of SLFN12 by PDE3A modulators, where early work identified PDE3A modulators, such as DNMDP, as cancer-selective cytotoxic agents that require co-expression of SLFN12, implicating this protein–protein interaction as a neomorphic driver of cell death [29]. The gene discussed is PDE3A; the disease is cancer.