We have recently described a high-throughput FRET screen that identified asparagine-containing linkers that are rapidly cleaved in lysosomal extracts. Unlike traditional ADC linkers that are cleaved by cathepsins, these linkers are cleaved by asparaginyl endopeptidase, also known as legumain. With the support of newly announced funding from the NIH (R01 GM144450-01), we are exploring the utility of legumain-cleavable linkers in ADC technology. Unlike traditional ValCit containing linkers, our linkers are not cleaved by neutrophil elastase, and therefore have the potential for decreased neutropenia and improved tolerability in humans. Legumain is also known to be secreted into the tumor microenvironment, and we are also interested to know if legumain-cleavable linkers may offer opportunities for extracellular payload release for non-internalizing ADC targets.