PLTP (phospholipid transfer protein) is a plasma glycoprotein that mediates bidirectional transfer of amphipathic lipids between circulating lipoproteins. Its primary function involves shuttling phospholipids and free cholesterol from triglyceride-rich lipoproteins (VLDL and LDL) to HDL, while also facilitating phospholipid exchange among triglyceride-rich lipoproteins themselves 1. PLTP transfers diverse lipid substrates including phosphatidylcholine, sphingomyelin, diacylglycerol, and cerebroside, and exists in two plasma forms—one catalytically active and one inactive 1. Mechanistically, PLTP plays a critical role in HDL remodeling by modulating size and composition, converting HDL to pre-beta-HDL forms 2. It also facilitates reverse cholesterol transport, enabling cholesterol uptake from peripheral tissues for hepatic degradation 1. Clinically, PLTP elevation associates with metabolic dysfunction: activity increases in type 1 and type 2 diabetes, obesity, and insulin resistance 2. Elevated PLTP levels correlate with hypertriglyceridemia and may contribute to atherogenesis through increased apolipoprotein B-containing lipoprotein production 3. Notably, PLTP functions as a p53 target gene involved in tumor suppression and ferroptosis regulation 4, and evidence demonstrates its role in innate immunity by neutralizing bacterial lipopolysaccharides during sepsis 5. Despite its complex, sometimes contradictory effects on cardiovascular risk, PLTP represents an emerging therapeutic target for inflammatory and infectious diseases.