Cereblon (CRBN) is a substrate recognition protein in the E3-ligase ubiquitin 
complex. The binding target of CRBN varies according to tissues and cells, and 
the protein regulates various biological functions by regulating tissue-specific 
targets. As new endogenous targets of CRBN have been identified over the past 
decade, the physiological and pathological functions of CRBN and its potential 
as a therapeutic target in various diseases have greatly expanded. For this 
purpose, in this review article, we introduce the basic principle of the 
ubiquitin-proteasome system, the regulation of physiological/pathological 
functions related to the endogenous substrate of CRBN, and the discovery of 
immunomodulatory imide drug-mediated neo-substrates of CRBN. In addition, the 
development of CRBN-based proteolysis-targeting chimeras, which has been 
actively researched recently, and strategies for developing therapeutic agents 
using them are introduced. These recent updates on CRBN will be useful in the 
establishment of strategies for disease treatment and utilization of CRBNs in 
biomedical engineering and clinical medicine.