Mechanism: MoDE mediated endocytosis is dependent on clathrin, but not LRP1. To explore the downstream trafficking of streptavidin upon MoDE 3-mediated endocytosis, we co-stained bEnd.3 cells for early endosome marker (EEA1) and lysosome marker (LAMP1). Colocalization was observed with LAMP1, demonstrating trafficking of streptavidin to the lysosome (Figure ). No colocalization was observed with EEA1 at the 24h timepoint (Supp. Figure ). As anticipated, no internalization of streptavidin was observed with MoDE 6 and no colocalization was observed with a rabbit isotype control antibody (Supp. Figure ). The subcellular localization of streptavidin in lysosomes combined with the appearance of a low molecular weight AF488-labeled degradation band supports our hypothesis that MoDE can act as a degrader of extracellular proteins by way of lysosomal proteases.