Model of TFEB- and trehalose-induced atheroprotection in macrophages. Left: Overexpression of TFEB, a transcription factor master regulator of autophagy-lysosome biogenesis, functionally drives this system in plaque macrophages. Trehalose is an autophagy-inducing disaccharide capable of inducing TFEB through mechanisms potentially involving acute perturbation of lysosomal function. Right: Enhanced function of the autophagy-lysosome system in macrophages attained with TFEB or trehalose results in atheroprotection associated with increased protein aggregate clearance, reduced apoptosis, and reduced IL1B production.