The cell surface receptor Protease-activated receptor 2 (PAR2) has recently been postulated to be involved in several critical pathways in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) progression where it triggers inflammation, fibrosis, and hepatocellular necrosis. Rana et al. found that PAR2 expression levels in hepatocytes significantly increase with disease progression in patients diagnosed with NAFLD and/or NASH. Mechanistic studies identified downstream effectors of cholesterol homeostasis and lipid metabolism. Together, these data indicate that blocking the activity of PAR2 may have broad salutary effects on cholesterol and lipid metabolism in NAFLD and NASH.