HMGCR and metabolic dysfunction-associated steatotic liver disease: In NAFLD, hepatic cholesterol homeostasis is imbalanced, resulting in elevated levels of hepatic cholesterol.389 This dysregulation may involve multiple metabolic pathways, including activation of cholesterol biosynthetic pathway (elevated expression and activity of SREBP2 and HMGCR), and cholesterol de-esterification (enhanced hydrolysis of CE to FC by hepatic neutral CE hydrolase), and reduced cholesterol export and BA synthesis (reduced expression of ABCG8 and CYP7A1).70,384,390,391 However, the contributions of these pathways to NAFLD need to be further explored.