In recent years, targeted protein degradation (TPD) technology has attracted great attention as a new drug discovery modality. TPD is a method to degrade and remove target proteins in cells by using compounds called degraders that utilize the endogenous protein degradation machinery. Given their unique mode of action, degraders are expected to be effective even against classically undruggable targets, such as nonenzymatic proteins and aggregation-prone proteins. Ubiquitin-proteasome system (UPS)-harnessing degraders termed proteolysis targeting chimeras (PROTACs), which are chimeric molecules composed of a ubiquitin ligase ligand and a ligand for the protein of interest (POI), have been most actively studied degraders and many PROTACs have already entered Phase I to III clinical trials. PROTACs are also used as chemical protein knockdown tools as alternatives to RNA interference, and have contributed to biological research. The emergence of PROTACs has already established that TPD technology is a promising approach, especially for hard-to-drug targets, and has led to the development of other TPD technologies such as hydrophobic tagging, which harnesses protein quality control machinery, and methods exploiting lysosomal degradation machineries, including AUTACs, ATTECs, AUTOTACs, and LYTACs. In 2022, Clausen et al. developed BacPROTAC, a degrader utilizing unique degradation machinery in gram-positive bacteria, for TPD in bacteria. This study pioneered the use of protein degradation machineries other than UPS and lysosomes.