CRBN and nervous system disorder: In 2013, Arvinas was founded as the first company dedicated to developing PROTACs for cancer and neurological diseases.73 The following year, studies revealed that lenalidomide, a therapeutic agent for myeloma, induces cereblon (CRBN)-mediated degradation of the transcription factors IKZF3 and IKZF1, elucidating its mechanism of action in MM and other B-cell malignancies.74,75 In 2014, a novel peptide-based strategy was also introduced, leveraging the chaperone-mediated autophagy (CMA) pathway to enable the reversible, dose-dependent and time-dependent degradation of native proteins.