Significant uptake of streptavidin was observed in both cell lines, with MFI values of the knockout cell line approximately triple those in the LRP1+ line. Furthermore, LRP1 expression in four different cell lines was measured by western blot and no correlation with MoDE-mediated streptavidin uptake was observed (Figure , Supp. Figure ). Taken together, these data suggest that MoDE-mediated endocytosis and degradation is LRP1 independent, engaging an alternative receptor for internalization and lysosomal degradation of the target protein. This endocytic profile clearly differentiates our approach from recently-published LRP1 targeting LYTACs where RAP and LRP1 knock out reduced efficacy of the bifunctional molecule. Experiments to identify the mechanisms underpinning this activity are ongoing.