CRBN ligands, which have become increasingly popular as E3 ligase ligands, are important in designing PROTACs (Proteolysis Targeting Chimeras) and molecular glue degraders, aiding in targeted protein degradation. CRBN, part of the CRL4 E3 ubiquitin ligase complex, binds to specific proteins and promotes their degradation, a process essential for cell regulation and apoptosis. In multiple myeloma (MM) treatment, drugs targeting CRBN, like thalidomide and lenalidomide, show effectiveness by altering substrate specificity of CRBN, targeting tumor-associated proteins for degradation. CRBN-based PROTACs are emerging as promising cancer treatments by directing CRBN to target proteins for degradation. Biocytogen has developed the B-hCRBN mouse model, engineered to express human CRBN instead of the mouse version by inserting the full-length humanCRBNCDS into the mouseCrbnexons 2-3. Expression of human CRBN mRNA and proteins were exclusively detected in homozygous humanized mice and these mice also demonstrated increased IL2 production in CD4+ T cells in response to lenalidomide treatment, confirming successful generation of the model. In summary, B-hCRBN mice are effective tool for preclinicalin vivoefficacy and safety evaluation of CRBN-targeted drugs, including CRBN-based small molecules, molecular glues, and PROTAC drugs.