Platelets play a critical role in the interplay between hyperlipidaemia and atherosclerosis. Hyperlipidaemia, particularly elevated levels of low-density lipoprotein (LDL), contributes to atherosclerosis by promoting platelet activation and dysfunction. Platelets, in turn, influence lipid metabolism and atherogenesis through various mechanisms, including the modulation of LDL oxidation, foam cell formation, and lipid accumulation. Native LDL (nLDL) and oxidized LDL (oxLDL) are key pro-atherosclerotic components that bind to specific platelet receptors, such as ApoE-R2 and scavenger receptors (CD36, LOX-1, SR-A1), leading to platelet activation and signaling pathways that enhance atherogenesis. OxLDL has a more pronounced effect on platelet activation and can prime platelets for further activation by other agonists. Platelet-derived factors, such as platelet factor 4 (PF4) and transforming growth factor β (TGFβ), also regulate lipid metabolism and atherosclerosis. PCSK9, a platelet-derived protein, influences LDL metabolism by modulating LDL receptor (LDLR) degradation and uptake. Hypolipidemic and antiplatelet drugs have pleiotropic effects, with statins reducing platelet activation and PCSK9 inhibitors influencing LDL levels and platelet function. The interplay between platelets and hyperlipidaemia is complex, with platelets contributing to both the progression and modulation of atherosclerosis. Understanding this interaction is crucial for developing therapeutic strategies targeting atherosclerotic diseases.Platelets play a critical role in the interplay between hyperlipidaemia and atherosclerosis. Hyperlipidaemia, particularly elevated levels of low-density lipoprotein (LDL), contributes to atherosclerosis by promoting platelet activation and dysfunction. Platelets, in turn, influence lipid metabolism and atherogenesis through various mechanisms, including the modulation of LDL oxidation, foam cell formation, and lipid accumulation. Native LDL (nLDL) and oxidized LDL (oxLDL) are key pro-atherosclerotic components that bind to specific platelet receptors, such as ApoE-R2 and scavenger receptors (CD36, LOX-1, SR-A1), leading to platelet activation and signaling pathways that enhance atherogenesis. OxLDL has a more pronounced effect on platelet activation and can prime platelets for further activation by other agonists. Platelet-derived factors, such as platelet factor 4 (PF4) and transforming growth factor β (TGFβ), also regulate lipid metabolism and atherosclerosis. PCSK9, a platelet-derived protein, influences LDL metabolism by modulating LDL receptor (LDLR) degradation and uptake. Hypolipidemic and antiplatelet drugs have pleiotropic effects, with statins reducing platelet activation and PCSK9 inhibitors influencing LDL levels and platelet function. The interplay between platelets and hyperlipidaemia is complex, with platelets contributing to both the progression and modulation of atherosclerosis. Understanding this interaction is crucial for developing therapeutic strategies targeting atherosclerotic diseases.