The accumulation of lipids in the arterial intima, inflammation, cell proliferation, and cell death is a major factor that determines the progression of atherosclerosis. Macrophages play a central role in all of these processes during the development of atherosclerosis. Macrophages are, as their name suggests, professional phagocytes whose phagocytic function is entirely dependent on lysosomes. Recent research has shown that lysosomes have much more complex functions than previously known, including nutrient and energy sensing, the regulation of autophagy, the initiation of cell death, and important roles in signaling pathways involved in many chronic inflammatory conditions and even the development of tumors (Conus and Simon 2008; Dubland and Francis 2015; Sergin et al. 2015; Perera and Zoncu 2016; Zhang et al. 2021).