Contradictory Effects on Hepatocytes in ASMD

Acid sphingomyelinase deficiency is a lysosomal storage disease that is characterized by the systemic accumulation of sphingomyelin in cells. This condition is frequently associated with hepatomegaly and hepatic dysfunction, with 91.4% of patients showing clinically relevant signs of liver involvement. Both clinical observations and experimental models show excessive sphingomyelin accumulation in hepatocytes. Studies using ASMD models have yielded conflicting results, showing hepatoprotective effects on one hand and detrimental effects on the other. Murine models demonstrated hepatoprotective effects of ASMD due to the modulation of endoplasmic reticulum stress. Patients with ASMD exhibit signs of impaired autophagy, which can lead to the accumulation of damaged cellular components and metabolic dysfunction. Furthermore, patients exhibit disrupted lipid metabolism, highlighting the dysfunction of hepatic lipid homeostasis. This review explores the involvement of ASMD in hepatocytes to better understand the disease mechanisms and possible therapeutic approaches.