Genetics
Lp(a) levels are driven mainly by how much the liver makes, not how fast it clears, redirecting drug development toward blocking production, a review (Curr Opin Lipidol 2022)
Original title: Understanding the ins and outs of lipoprotein (a) metabolism
This review by Boffa and Koschinsky synthesises current understanding of Lp(a) particle assembly and clearance. Lp(a) assembly occurs in two steps: a noncovalent, lysine-dependent interaction between apo(a) and apoB-100 inside hepatocytes, followed by extracellular covalent linkage. The authors conclude that Lp(a) production rate, rather than its clearance rate, primarily explains the inverse relationship between apo(a) isoform size and Lp(a) levels, with catabolism playing a role mainly for larger isoforms; factors affecting apoB-100 secretion also affect apo(a) secretion. The identity of the key hepatic receptors mediating Lp(a) clearance in vivo remains unclear, with a role for the LDL receptor apparently limited to conditions of low LDL and maximally upregulated LDL receptor expression. The authors conclude that therapies inhibiting Lp(a) production are likely to be more effective than those targeting its removal from circulation.
Original abstract
Purpose Of Review: This review summarizes our current understanding of the processes of apolipoprotein(a) secretion, assembly of the Lp(a) particle and removal of Lp(a) from the circulation. We also identify existing knowledge gaps that need to be addressed in future studies.
Recent Findings: The Lp(a) particle is assembled in two steps: a noncovalent, lysine-dependent interaction of apo(a) with apoB-100 inside hepatocytes, followed by extracellular covalent association between these two molecules to form circulating apo(a).The production rate of Lp(a) is primarily responsible for the observed inverse correlation between apo(a) isoform size and Lp(a) levels, with a contribution of catabolism restricted to larger Lp(a) isoforms.Factors that affect apoB-100 secretion from hepatocytes also affect apo(a) secretion.The identification of key hepatic receptors involved in Lp(a) clearance in vivo remains unclear, with a role for the LDL receptor seemingly restricted to conditions wherein LDL concentrations are low, Lp(a) is highly elevated and LDL receptor number is maximally upregulated.
Summary: The key role for production rate of Lp(a) [including secretion and assembly of the Lp(a) particle] rather than its catabolic rate suggests that the most fruitful therapies for Lp(a) reduction should focus on approaches that inhibit production of the particle rather than its removal from circulation.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.