Acid sphingomyelinase, a specific mechanism of ceramide generation, is required for the activation of key pathways that regulate hepatic steatosis and fibrosis, including endoplasmic reticulum stress and autophagy, and targeting acid sphingomyelinase can increase methionine cycling and phosphatidylcholine metabolism to slow the progression of NASH 115. Here, SMPD1 is linked to metabolic dysfunction-associated steatohepatitis.