1. Insights in the Understanding of Cholesterol Metabolism:

2. Table of Contents

3. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Pathway

4. Hepatic LDLRs Play a Central Role in Cholesterol Homeostasis

5. Recycling of LDLRs Enables Efficient Clearance of LDL-C Particles

7. Genetic Variants of PCSK9 Demonstrate Its Importance in Regulating LDL Levels

8. Gain-of-Function Mutations in PCSK9 Cause Familial Hypercholesterolemia*†

9. Loss-of-Function Mutations in PCSK9 Are Associated With Decreased LDL-C

11. Expression of PCSK9 Depends on Intracellular Cholesterol Levels

12. Summary

13. Genetic Variants of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)

14. PCSK9 Mutations Are Involved in Familial Hypercholesterolemia

15. PCSK9 is a Key Regulator of LDLR Recycling

16. Regulation of PCSK9 is Dynamic

17. Genetic Variants of PCSK9 Demonstrate its Importance in Regulating LDL Levels

18. PCSK9 GOF Mutations

19. Clinical Outcomes Associated With Genetic Mutations for Gain of PCSK9 Function

20. Case Reports Highlight Hypercholesterolemia Associated With PCSK9 GOF Mutations

21. GOF Mutations Are Associated With Increased ApoB-Containing Lipoproteins in Humans

22. PCSK9 GOF Mutations Associated With FH*1

23. PCSK9 LOF Mutations

24. Clinical Outcomes Associated With Genetic Mutations for Loss of PCSK9 Function

25. PCSK9 LOF Mutations Are Associated With Decreased Plasma LDL-C Concentrations

26. PCSK9 LOF Mutations and Variants Associated With Hypocholesterolemia

27. PCSK9 LOF Compound Heterozygote With No Detectable Circulating PCSK9

28. PCSK9C679X-Associated Cholesterol Lowering in a Population With Low LDL-C

29. Summary