CRBN encodes cereblon, a substrate recognition component of the CUL4-DDB1-CRBN E3 ubiquitin ligase complex that mediates ubiquitination and proteasomal degradation of target proteins including MEIS2, ILF2, and GLUL 12. CRBN is essential for normal limb development and fibroblast growth factor FGF8 expression through degradation of key regulatory proteins 34. In the nervous system, CRBN maintains cognitive function by negatively regulating large-conductance calcium-activated potassium (BK) channels in excitatory neurons, supporting presynaptic glutamate release and memory formation 56. CRBN also suppresses TLR4 signaling by inhibiting ECSIT ubiquitination through TRAF6 interaction 7. Clinically, CRBN is a target of thalidomide and its derivatives (lenalidomide, pomalidomide), which bind CRBN and reprogram its substrate specificity to induce degradation of neosubstrates like IKZF1 and IKZF3 48. This molecular glue mechanism underlies both therapeutic benefits in multiple myeloma and teratogenic effects on limb development 38. CRBN-based PROTACs (proteolysis-targeting chimeras) represent emerging therapeutics for cancer, cardiovascular, immune, and neurodegenerative diseases 9. Mutations in CRBN cause autosomal recessive intellectual developmental disorder type 2, highlighting its critical role in cognitive development.