Proprotein convertase subtilisin/KEXIN type 9 (PCSK9) is the ninth member of the proprotein convertase family and released into the bloodstream. It reduces the availability of low-density lipoprotein receptors and leads to the accumulation of low-density lipoprotein cholesterol in plasma, thereby promoting the development of atherosclerotic plaques and thrombotic events. In addition to its classical pathway, recent studies have demonstrated multiple non-classical pathways by which PCSK9 influences the development of atherosclerosis-related diseases, including participation in inflammatory responses, regulation of autophagy and cell apoptosis, promotion of platelet activation and thrombus formation, etc. This article provides an overview of the latest progress in the molecular mechanism by which PCSK9 affects atherosclerotic diseases through non-lipid-dependent pathways.