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The mechanisms of quality control for extracellular proteins are still poorly understood. In this issue, Itakura et al. (2020. J. Cell. Biol.https://doi.org/10.1083/jcb.201911126) show that upon binding to misfolded proteins, the extracellular chaperone clusterin is internalized via the heparan sulfate receptor to undergo lysosomal degradation.

Heparan sulfate and clusterin: Cleaning squad for extracellular protein degradation