It has been long recognized that cholesterol is a critical molecule in mammalian cell biology, primarily for its contribution to the plasma membrane’s composition and its role in assuring proper transmembrane receptor signaling as part of lipid rafts. Efforts have also been made to characterize the cholesterol biosynthetic pathway, cholesterol homeostasis, and cholesterol-derived metabolites in order to gain insights into their dysregulation during metabolic diseases. Despite the central role cholesterol metabolism plays in shaping human health, its regulation during immune activation, such as immune response to pathogens or autoimmune/autoinflammatory diseases, is poorly understood.