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. 2021 Oct 15;8:764038. doi: 10.3389/fcvm.2021.764038

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Copyright © 2021 Xia, Peng, Gu, Wang, Wang and Zhang.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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PCSK9, LDLR, and MHCI. PCSK9 is auto-cleaved in the ER. Mature PCSK9 is transported to the Golgi and then secreted. PCSK9 binds to LDLR and MHCI on the cell surface. After, the complex is delivered to endosomes via endocytosis and then transported to the lysosome for degradation. LDLR binds to its ligands such as LDL, VLDL, and Lp(a) and then the receptor/ligand complex enters cells via receptor-mediated endocytosis and is delivered to the endosome. In the acidic endosomal environment, the ligand, such as LDL, is released from LDLR and transported to the lysosome for degradation. LDLR is recycled to plasma membrane. PCSK9-promoted degradation of LDLR increases plasma levels of LDL and Lp(a). Pro, prodomain; CAT, catalytic domain; CTD, C-terminal domain.