Abstract 2651 PNPLA3-I148M is a Neomorph that Interferes with Two Primary Hepatic Triglyceride Clearance Pathways
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive metabolic disorder that begins with aberrant triglyceride accumulation in the liver and can lead to cirrhosis and cancer. A common variant in the gene PNPLA3, encoding the protein PNPLA3-I148M (hereafter called “I148M”), has been identified in several genome-wide association studies (GWAS) as the strongest known genetic risk factor for MASLD to date. Despite its discovery twenty years ago, the function of PNPLA3, and now the role of I148M, remain unclear.
Authors
- Ingrid C. Rulifson (ORCID: https://orcid.org/0000-0003-3251-3989)
- Mark S. Ladinsky (ORCID: https://orcid.org/0000-0002-1036-3513)
- David H. Sherman (ORCID: https://orcid.org/0000-0001-8334-3647)
- Preston Fordstrom (ORCID: https://orcid.org/0000-0002-4562-7128)
- Raymond J. Deshaies (ORCID: https://orcid.org/0000-0002-3671-9354)
- John Ferbas (ORCID: https://orcid.org/0000-0003-4087-4629)
- Edward L. LaGory (ORCID: https://orcid.org/0000-0002-0552-1695)
- Lei Liu (ORCID: https://orcid.org/0000-0002-0500-6239)
- Jiansong Xie
Institutions
- Amgen (United States) (US)
Publication Details
- Journal
- Journal of Biological Chemistry
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1016/j.jbc.2025.109441
- Primary Topic
- Liver Disease Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00