FBXO22 is a promising E3 ubiquitin ligase for targeted protein degradation

Targeted protein degradation (TPD) is an exciting new strategy to destroy, rather than simply inhibit, therapeutic targets of interest. Degrader molecules function by recruiting protein targets to E3 ubiquitin ligases, resulting in target polyubiquitination and destruction. Although there are >600 E3s, relatively few, notably CRBN and VHL, are routinely used for TPD applications in either academic or clinical settings. An up-and-coming ligase on the TPD scene is FBXO22, which has multiple distinct features when compared to other commonly used E3s. Here, we highlight the native functions of FBXO22 and the chemical matter (degraders) used to repurpose FBXO22's ubiquitination activity. As FBXO22 is overexpressed in a variety of cancers, this may provide a therapeutic window to destroy targets selectively in cancer cells. Taken together, FBXO22 fulfills a necessary void in the TPD field and provides a new approach to develop novel cancer therapeutics.