The CRBN gene, located on chromosome 3, exhibits broad expression across diverse tissues, including the brain, kidney, muscle, and immune cell populations such as monocytes, macrophages, dendritic cells, and B lymphocytes ^[1]. This gene encodes cereblon, a protein that functions as a key substrate receptor within the CRL4-CRBN E3 ubiquitin ligase complex. This complex mediates the ubiquitination and subsequent proteasomal degradation of specific target proteins, thereby regulating crucial cellular processes encompassing protein homeostasis, ion transport, and AMPK signaling ^[1-2]. Notably, mutations in CRBN are implicated in autosomal recessive nonsyndromic intellectual disability ^[2]. Furthermore, Cereblon protein serves as a primary molecular target for targeted protein degradation (TBD) therapy by specifically modulating the enzymatic activity of the CRL4-CRBN complex and altering its substrate recognition properties, thereby enabling the selective degradation of specific transcription factors. This molecular mechanism has emerged as a critical theoretical foundation for the clinical treatment of malignant hematological malignancies such as multiple myeloma, leading to the development of diverse therapeutic modalities including molecular glues and proteolysis targeting chimeras (PROTACs) ^[3-5].

BALB/c-hCRBN mice are humanized models generated by gene editing technology, in which the exon 2 to partial intron 2 of the mouse Crbn gene was replaced in situ with the Exon 2~11 of the coding sequence (CDS) of human CRBN gene. This model can be used to study the pathological mechanisms and therapeutic methods of autosomal recessive nonsyndromic intellectual disability and multiple myeloma and other hematological cancers, as well as the screening, development, and preclinical efficacy and safety evaluation of CRBN-based targeted protein degradation (TBD) therapies.