Targeting PKLR in liver diseases
The pyruvate kinase liver/red blood cell (PKLR) gene critically regulates hepatic glucose and lipid metabolism, driving metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC) pathogenesis via altered glycolysis and lipid metabolism, and mitochondrial dysfunction.
PKLR expression shows sex-specific effects, with higher expression levels in men linked to increased MASLD severity, highlighting the need for personalized approaches in managing metabolic diseases.
Recent progress in developing PKLR inhibitors, including small molecules, holds promise for targeted treatments of MASLD and HCC, with preclinical studies demonstrating potential for reducing liver fat and improving metabolic profiles.
https://www.cell.com/trends/endocrinology-metabolism/fulltext/S1043-2760(25)00054-2
