Early studies suggested the existence of an hepatic receptor that is involved in the clearance of serpin:enzyme complexes. Subsequent work has identified this receptor as the LDL receptor-related protein 1 (LRP1). LRP1 is a multifunctional receptor that serves to transport numerous molecules into the cell via endocytosis and also serves as a signaling receptor. LRP1 plays diverse roles in biology, including roles in lipoprotein metabolism, regulation of protease activity, activation of lysosomal enzymes, and cellular entry of bacterial toxins and viruses. Deletion of the Lrp1 gene leads to lethality in mice, revealing a critical, but as of yet undefined, role in development. Its identification as a receptor for serpin:enzyme complexes confirms a major role for LRP1 in regulating protease activity.
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