Clinical investigations demonstrate that NAFLD/NASH patients exhibit enhanced nuclear SREBP2 localization, accompanied by increased HMGCR transcriptional/translational activity and phosphorylation, while showing reduced LDLR expression and impaired ABC transporter (ABCA1, ABCG1, ABCG5) function. Here, HMGCR is linked to metabolic dysfunction-associated steatohepatitis.