An LCAT test measures the activity or concentration of lecithin-cholesterol acyltransferase, an enzyme your liver produces that plays a central role in how your body processes cholesterol. The test is typically ordered when a doctor suspects a rare genetic condition affecting cholesterol metabolism, or as part of a workup for unusually low HDL cholesterol that doesn’t respond to lifestyle changes. It’s a specialized blood test, not part of routine cholesterol screening.
What LCAT Does in Your Body
LCAT is an enzyme that converts free cholesterol into a packaged form called cholesteryl ester. It does this by pulling a fatty acid off a phospholipid molecule and attaching it to cholesterol. That chemical change makes the cholesterol much more water-repellent, causing it to move from the surface of HDL particles into their core. This transformation is what turns small, immature HDL particles into the larger, spherical HDL particles that make up most of the HDL in your blood.
This matters for two reasons. First, the larger HDL particles are more stable in your bloodstream. Small, immature HDL gets filtered out by the kidneys relatively quickly, so without LCAT converting them, HDL levels drop. Second, LCAT keeps the cholesterol-removal process running. HDL works by pulling cholesterol away from cells in your arteries and other tissues, a process called reverse cholesterol transport. Once LCAT packages that cholesterol into the core of the HDL particle, it can’t leak back out to the cells it came from. Without this step, HDL would quickly fill up and stop accepting new cholesterol.
Why the Test Is Ordered
Doctors order an LCAT test primarily when they suspect a genetic deficiency of the enzyme. This suspicion usually arises from a combination of very low HDL cholesterol (below the 5th percentile), cloudy corneas, or unexplained anemia. The test may also be part of an evaluation when kidney disease appears alongside abnormal cholesterol levels without another clear cause.
LCAT deficiency is inherited in an autosomal recessive pattern, meaning you need to receive a defective copy of the LCAT gene (located on chromosome 16) from both parents. It comes in two forms, and the test helps distinguish between them:
- Familial LCAT deficiency (FLD): Complete loss of enzyme activity. This causes extremely low HDL, corneal cloudiness that often begins in early childhood, hemolytic anemia (where red blood cells break down prematurely), and progressive kidney damage. About 75% of people with FLD develop hemolytic anemia, and roughly 40% show significant kidney impairment. The average age of diagnosis is around 41.
- Fish-eye disease (FED): Partial loss of enzyme activity. The enzyme still works on LDL and VLDL particles but not on HDL, so HDL particles contain only about 20% cholesteryl ester compared to the normal 75 to 80%. People with FED develop corneal opacities and low HDL but are largely spared the kidney problems. However, they have a notably higher rate of premature coronary heart disease, around 28% compared to less than 1% in FLD. Fish-eye disease tends to be diagnosed later, at an average age of 55.
How the Test Works
The LCAT test requires a blood draw, and the plasma sample is sent to a specialized laboratory. There are a few different methods labs use to measure enzyme activity. The traditional approach uses radioactively labeled cholesterol as a substrate and measures how much of it gets converted to cholesteryl ester over a set period. In healthy individuals, this method yields a reference range of roughly 56 to 149 nmol/mL/h.
Newer fluorescent assays use a specially tagged cholesterol molecule and measure the same conversion. These tests report a reference range of approximately 4.6 to 24.1 Unit/mL/h in healthy subjects. Genetic testing of the LCAT gene can confirm a diagnosis and identify the specific mutation, which helps predict whether someone has the complete or partial form of the deficiency.
What Low LCAT Activity Does to the Body
When LCAT activity is very low or absent, cholesterol can’t be properly packaged into HDL. This causes a buildup of free cholesterol in the blood and tissues, with several downstream effects.
The corneal cloudiness that characterizes both forms of LCAT deficiency comes from cholesterol deposits. These appear as small grayish dots scattered across the cornea, typically starting in childhood for FLD. Over time, the cloudiness worsens and can seriously impair vision.
The anemia in FLD happens because excess free cholesterol gets incorporated into red blood cell membranes, making them fragile and prone to breaking apart. This leads to pale skin, fatigue, and weakness.
Kidney damage, the most serious complication of complete LCAT deficiency, involves an abnormal lipoprotein particle called lipoprotein X. This particle, enriched with unesterified cholesterol, accumulates in the tiny blood vessels of the kidneys. It’s cytotoxic and pro-inflammatory, damaging the filtering structures and causing progressive loss of kidney function. More than half of FLD patients develop protein in their urine, a sign of kidney damage.
Treatment Options
There is no widely available cure for LCAT deficiency yet, but several approaches are in development. The most advanced is enzyme replacement therapy using a lab-made version of human LCAT, which has completed early-phase clinical trials. In one patient treated over approximately seven months with weekly or twice-weekly infusions, HDL particles rapidly matured from small discoidal forms into large spherical ones. Anemia improved significantly, and kidney function stabilized.
Gene therapy using viral vectors that deliver a working copy of the LCAT gene to liver cells is another active area of investigation. Researchers are also exploring the possibility of taking a patient’s own fat cells, engineering them to produce LCAT, and reimplanting them.
On the pharmaceutical side, small-molecule LCAT activators that can be taken orally have shown promise in animal studies. At least one compound has demonstrated the ability to increase cholesterol packaging and slow atherosclerosis progression in mice.
In the meantime, management focuses on limiting dietary fat, avoiding smoking, and eating antioxidant-rich foods to help preserve whatever LCAT activity remains and protect kidney function. Patients with advanced kidney disease may eventually require dialysis or transplantation.