LCAT (lecithin-cholesterol acyltransferase) is the sole plasma enzyme catalyzing cholesterol esterification, central to extracellular lipoprotein metabolism 1. Synthesized primarily in liver and secreted into plasma, LCAT converts free cholesterol and phosphatidylcholines to cholesteryl esters and lysophosphatidylcholines on HDL and LDL surfaces, facilitating reverse cholesterol transport 1. This esterification is essential for HDL maturation from discoidal to spherical particles 2. LCAT is also produced by cerebral astrocytes, where it esterifies cholesterol on APOE-containing lipoproteins, influencing CSF lipid composition [UniProt]. Beyond cholesterol metabolism, LCAT catalyzes platelet-activating factor inactivation and 24(S)-hydroxycholesterol esterification [UniProt]. LCAT deficiency impairs cholesterol homeostasis and is associated with fish-eye disease and familial LCAT deficiency. Recent evidence reveals LCAT's tumor-suppressive role: estrogen upregulates LCAT to enhance HDL-cholesterol production, suppressing hepatocellular carcinoma (HCC) development through cholesterol biosynthesis inhibition 3. Conversely, LCAT downregulation promotes HCC progression and lenvatinib resistance by enhancing triglyceride catabolism and fatty acid oxidation 4. Genetic polymorphisms in LCAT (rs2292318) correlate with HDL-cholesterol levels and acute coronary syndrome risk 5. LCAT emerges as both a prognostic biomarker and potential therapeutic target for cardiovascular and malignant disease.