Editing Low-density lipoprotein (section)

===Transport into the cell===
When a cell requires more cholesterol than its [[HMG-CoA reductase|HMG-CoA]] pathway can produce, it synthesizes the necessary [[LDL receptor]]s as well as [[PCSK9]], a [[proprotein convertase]] that marks the LDL receptor for degradation.<ref>{{cite journal |last1=Zhang |first1=Da-Wei |last2=Garuti |first2=Rita |last3=Tang |first3=Wan-Jin |last4=Cohen |first4=Jonathan C. |last5=Hobbs |first5=Helen H. |title=Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor |journal=Proceedings of the National Academy of Sciences |date=2 September 2008 |volume=105 |issue=35 |pages=13045–13050 |doi=10.1073/pnas.0806312105 |bibcode=2008PNAS..10513045Z |pmc=2526098 |pmid=18753623 |doi-access=free}}</ref> LDL receptors are inserted into the plasma membrane and diffuse freely until they associate with [[clathrin]]-coated pits. When LDL receptors bind LDL particles in the bloodstream, the clathrin-coated pits are endocytosed into the cell.{{cn|date=November 2024}}

Vesicles containing LDL receptors bound to LDL are delivered to the [[endosome]]. In the presence of low [[pH]], such as that found in the endosome, LDL receptors undergo a conformation change, releasing LDL. LDL is then shipped to the [[lysosome]], where [[cholesterol ester]]s in the LDL are [[Hydrolysis|hydrolysed]]. LDL receptors are typically returned to the plasma membrane, where they repeat this cycle. If LDL receptors bind to PCSK9, however, transport of LDL receptors is redirected to the lysosome, where they are degraded.<ref>{{Cite journal |vauthors=Santulli G, Jankauskas SS, Gambardella J |date=May 2021 |title=Inclisiran: a new milestone on the PCSK9 road to tackle cardiovascular risk |journal=Eur Heart J Cardiovasc Pharmacother |volume=7 |issue=3 |pages=e11–e12 |doi=10.1093/ehjcvp/pvab014 |pmid=33655296 |doi-access=free}}</ref>