Heterobifunctional degraders known as Proteolysis Targeting Chimeras (PROTACs) are well-established as powerful tools for small molecule-directed protein degradation. These two-headed molecules consist of a ligand for a protein of interest joined to an E3 ligase-recruiting motif via a linker that plays an important role in directing the formation of a non-physiological ternary complex between an E3 ligase and the protein of interest in cells (Figure ). PROTACs thereby promote intracellular polyubiquitination and subsequent proteasome-dependent degradation of the targeted protein in a unique posttranslational mode of action, which complements traditional gene and siRNA protein silencing strategies. Moreover, the catalytic mechanism of action, versatility of the approach and potential to degrade targets lacking enzymatic activity has prompted major drug discovery efforts both in academia and industry. We hypothesized that PROTAC-mediated protein knockdown could be achieved with an additional level of precision if placed under a conditional stimulus such as light. Since protein function is often regulated in time and space, light would represent a suitable tool to activate or deactivate degradation as light itself can be controlled both spatially and temporally. Moreover, the combination of PROTACs with light to degrade a disease-relevant protein may offer some applications in the field of photopharmacology. In previous reports, light-induced protein degradation has been carried out via the use of optogenetic methods which rely primarily on degron sequences borrowed from the plant realm. However, lightmediated small molecule regulation of mammalian proteins has not been explored extensively until very recently. For example, whilst this manuscript was in preparation, Xue et al. reported a caged PROTAC approach whereby photocleavable 4,5-dimethoxy-2-nitrobenzyl (DMNB) group was introduced to prevent binding of pan-bromodomain inhibitor JQ1 to BRD4. The same caging moiety was also attached to the immunomodulatory drug thalidomide to block the recruitment of E3 ligase cereblon for Bruton's tyrosine kinase (BTK) degradation. In both cases, proteolysis was observed only after uncaging of the PROTAC.