On a molecular level IMiDs bind the substrate receptor cereblon (encoded by the gene CRBN) of the CRL4CRBN E3 ubiquitin ligase and redirect it to degrade IKZF1/3 and CK1α, key dependencies in blood cancers.1,2 An alternative strategy to degrade proteins is to generate a bifunctional molecule, where an E3 ligase ligand is tethered to a target binder with a chemical linker creating a proteolysis targeting chimera (PROTAC).3 Both PROTACs and molecular glue degraders alter the interactome of the E3 ligase to induce recruitment and ubiquitination of specific target proteins (neosubstrates). The gene discussed is CRBN; the disease is hematopoietic and lymphoid system neoplasm.