Core Viewpoint - Targeted Protein Degradation (TPD) technologies, such as PROTAC, offer promising new avenues for drug development, but face challenges in degrading transmembrane proteins due to their reliance on degradation mechanisms that cannot access these proteins effectively [2][5]. Group 1: TPD Technologies and Challenges - Various TPD strategies have been developed for transmembrane proteins, including LYTAC, GlueTAC, and TransTAC, which open unprecedented research opportunities [2]. - These technologies depend on the Endosome-Lysosome pathway and are influenced by Recycling Endosomes, which tend to recycle transmembrane targets, thus reducing degradation efficiency [2]. - Most TPD strategies utilize large biomolecules like antibodies, while small molecule compounds may offer advantages such as easier delivery, lower costs, diverse application routes, longer shelf life, and typically non-immunogenic properties [2]. Group 2: ERADEC Development - A new TPD technology named ERADEC (ERAD-engaging Chimera) was developed by a research team from Fudan University and the Naval Medical University, which "hijacks" the ER-associated degradation (ERAD) mechanism to promote the ubiquitination and degradation of target proteins [3][6]. - The team discovered that the small molecule desonide can bind to the ER E3 ubiquitin ligase SYVN1, facilitating the ubiquitination and subsequent degradation of target proteins [6]. Group 3: Validation and Broader Implications - The ERADEC technology was validated using the PD-L1 protein, demonstrating efficient degradation through SYVN1 and ERAD dependency, outperforming widely used PD-L1 antibodies in tumor suppression effects in mouse models [7]. - The concept of ERADEC can be extended to other membrane proteins, indicating its potential as a universal platform technology for selective and efficient degradation of transmembrane proteins [9].