ABSTRACT
Ceramide is the most studied sphingolipid due to its emerging role as a second messenger that regulates multiple cellular functions. Acid sphingomyelinase (ASMase) functions as a specic mechanism of ceramide generation upon sphingomyelin hydrolysis at acidic compartments. In addition to its established role in apoptosis, recent evidence has shown a novel function of ASMase in liver brosis, endoplasmic reticulum (ER) stress, autophagy, and lysosomal membrane permeabilization, which impact the development of liver diseases. Moreover, ASMase regulates mitochondrial function, antioxidant defense, and reactive oxygen species (ROS) generation due to the stimulation of cholesterol trafcking to mitochondria by a mechanism involving ASMase-induced ER stress. In this chapter, we summarize the role of ASMase in Wilson disease, hepatic ischemia/reperfusion injury, and alcoholic and nonalcoholic fatty liver diseases. This evidence suggests that inhibiting ASMase may be of relevance in liver diseases in preventing ceramide generation and preserving lysosomal sphingomyelin content and function.
