If you have high lipoprotein(a), or Lp(a), you have probably been told there is not much you can do. Unlike LDL cholesterol, which can be influenced by diet, exercise, and medications like statins, Lp(a) is mostly inherited. For decades, research has focused on how Lp(a) is produced, largely through the LPA gene, but almost nothing was known about how it is cleared from the body. That has just changed.

In a groundbreaking 2025 study published in Atherosclerosis, Khan and colleagues used a CRISPR-based genome-wide knockout screen to identify the cellular machinery responsible for clearing Lp(a) from liver cells. This method allows researchers to disable nearly every gene in the genome, one at a time, and then measure how that affects a cell’s ability to take up fluorescently labeled Lp(a). The results were striking.

The top gene required for Lp(a) uptake was LDLR, which encodes the LDL receptor. This receptor is already well known for clearing LDL cholesterol and is the primary gene involved in familial hypercholesterolemia, a condition that causes early cardiovascular disease. But now it appears the LDL receptor is also central to how the body clears Lp(a).

They also found that disabling MYLIP, which encodes a protein called IDOL that normally degrades LDL receptors, led to increased Lp(a) uptake. More LDL receptors meant more Lp(a) being pulled out of circulation. This finding was consistent with data from large population biobanks showing that people with LDL receptor mutations tend to have higher Lp(a) levels.

Why does this matter for you? Because it may explain why some cholesterol-lowering drugs reduce Lp(a), and others do not. PCSK9 inhibitors, for example, prevent LDL receptor degradation and increase receptor availability on liver cells. These drugs consistently lower Lp(a) by about 25 to 45 percent. CETP inhibitors like obicetrapib also reduce Lp(a), likely by similar mechanisms.

Statins, on the other hand, are a puzzle. While they increase the number of LDL receptors, they often do not lower Lp(a) and in some cases raise it. This new study suggests that while the LDL receptor plays a role in Lp(a) clearance, other statin-induced pathways may interfere with that benefit.

Previously, scientists suspected another liver protein called SR-B1 might be responsible for Lp(a) uptake. This new data puts the LDL receptor front and center instead.

So here is what we now know. Your body likely uses the LDL receptor not just to clear LDL cholesterol but also to clear Lp(a). If you have high Lp(a), therapies that boost LDL receptor levels could help lower it. That includes PCSK9 inhibitors, and potentially others on the horizon. This also helps explain why individuals with familial hypercholesterolemia tend to have very high Lp(a) levels and greater cardiovascular risk.

This is a major step forward. For the first time, we have a clear look at how Lp(a) leaves the bloodstream. And that insight could finally lead to effective treatments for one of the most stubborn risk factors in cardiovascular disease.