The article reviews the recent advancements in three Ubiquitin-Proteasome System (UPS)-based technologies: molecular glue degraders, PROTACs (proteolysis-targeting chimeras), and DUBTACs (deubiquitinase-targeting chimeras). These technologies aim to promote protein degradation or stabilize disease-inhibitory proteins using the UPS. Molecular glue degraders, such as thalidomide and its analogs, aryl sulfonamides, and cyclin-dependent kinase (CDK) inhibitors, enhance the interaction between Ub ligases and targeted proteins, leading to their degradation. PROTACs consist of a ligand binding to the protein of interest (POI) and another ligand interacting with a Ub ligase, promoting the proximity and degradation of the POI. DUBTACs, a newly developed strategy, stabilize proteins by cleaving poly-Ub chains on the targeted proteins. The article discusses the mechanisms, applications, and future directions of these technologies, highlighting their potential in drug discovery and targeted protein homeostasis.The article reviews the recent advancements in three Ubiquitin-Proteasome System (UPS)-based technologies: molecular glue degraders, PROTACs (proteolysis-targeting chimeras), and DUBTACs (deubiquitinase-targeting chimeras). These technologies aim to promote protein degradation or stabilize disease-inhibitory proteins using the UPS. Molecular glue degraders, such as thalidomide and its analogs, aryl sulfonamides, and cyclin-dependent kinase (CDK) inhibitors, enhance the interaction between Ub ligases and targeted proteins, leading to their degradation. PROTACs consist of a ligand binding to the protein of interest (POI) and another ligand interacting with a Ub ligase, promoting the proximity and degradation of the POI. DUBTACs, a newly developed strategy, stabilize proteins by cleaving poly-Ub chains on the targeted proteins. The article discusses the mechanisms, applications, and future directions of these technologies, highlighting their potential in drug discovery and targeted protein homeostasis.