RNF146 and neoplasm: This could be achieved through the following possible approaches: developing proteolysis-targeting chimeras (PROTACs) for selective degradation of PARdU components and their positive regulators (Figure 5); conducting proteomics and CRISPR screens to identify new PARdU substrates and their interactions; designing iso-ADPr mimetics to disrupt RNF146-substrate interactions; and combining PARdU inhibitors with immune checkpoint blockade therapies to modulate PD-L1 degradation and enhance anti-tumor immunity.