“…However, the inverse situation of identifying the effector protease responsible for a specific cleavage event is much more challenging, and typically depends on time-consuming and costly screening strategies or bioinformatic approaches based on known protease substrate specificities 29,30 which are limited in their physiological relevance by spatiotemporal regulation of protease expression and/or activity. Activity-based probes (ABPs) that capture particular classes of proteases can resolve spatiotemporal changes in proteolytic activity and facilitate de novo discovery of proteases involved in specific physiological and pathological processes 31,32 . However, current ABP formats do not provide insights into substrates, necessitating extensive screening and proteomic analysis to demonstrate biological mechanism 32,33 .…”