| CD36 is a multifunctional class B scavenger receptor glycoprotein with a core molecular weight of about fifty-three kilodaltons that is heavily glycosylated and expressed on monocytes, macrophages, platelets, endothelial cells, adipocytes, and epithelial cells, where it mediates ligand uptake, signaling, and a broad range of physiological processes. CD36 features short N- and C-terminal cytoplasmic tails with acylated cysteines at both ends that promote membrane apposition, and key tyrosine and cysteine residues in the C-terminal tail that are critical for signaling. It contains two transmembrane domains and a large extracellular domain with multiple glycosylation sites and hairpin loops for ligand binding, and it localizes within cholesterol-rich lipid rafts and caveolae. Its primary functions include ligand-specific signaling and endocytosis. For example, binding oxidized low-density lipoprotein triggers activation of Src family kinases such as Lyn and Fyn, MAP kinases including p38 and JNK, Vav guanine nucleotide exchange factors, and Lyn-Vav-dynamin complexes, leading to Rac and Rho GTPase activation, reactive oxygen species production, cytoskeletal rearrangement, oxidized LDL internalization, foam cell formation, and migration inhibition in macrophages, which are key features of atherogenesis. Engagement with thrombospondin-1 activates Fyn, p38, and caspase-3, resulting in endothelial cell apoptosis and inhibition of angiogenesis. CD36 also mediates uptake of fatty acids and microbial patterns such as beta-glucans and lipoproteins, facilitating innate immunity, platelet reactivity, and metabolism. CD36 is involved in balancing lipid homeostasis, phagocytosis, thrombosis, and anti-angiogenic responses, and interacts with toll-like receptors, integrins, and tetraspanins to amplify signaling. Disease relevance of CD36 includes roles in atherosclerosis through foam cell formation, cardiomyopathy due to lipotoxicity, malaria by mediating infected erythrocyte cytoadherence, and cancer by promoting metastasis. |