[The role of the PNPLA3 gene rs738409 variant in the spectrum of metabolic dysfunction associated steatotic liver diseases].

Non-alcoholic fatty liver disease (NAFLD) - more recently referred to as metabolic dysfunction-associated steatotic liver disease (MASLD) - has become a widespread public health concern. Among the various factors contributing to its development and progression toward more severe forms (including steatohepatitis, liver fibrosis, cirrhosis, and hepatocellular carcinoma), a single nucleotide polymorphism in the PNPLA3 gene, resulting in an amino acid substitution, has emerged as one of the key genetic factors. Over the past two decades, this variant has been extensively studied. Current knowledge regarding both the clinical relevance of this variant and the role of its gene product in disease pathogenesis continues to expand, providing increasing insight into the physiological and pathological functions of PNPLA3 gene variants and their encoded protein isoforms. Although PNPLA3 genotyping is not yet part of routine diagnostics or therapeutic decision-making, the growing body of research and the variant's considerable effect size suggest potential future applications in prognostic assessment and therapeutic strategies - particularly within the framework of personalized medicine. The aim of this review is to provide a structured summary of the currently available published evidence, covering aspects of PNPLA3 functionality, biological mechanisms, clinical implications, and its potential utility in diagnostics, disease progression assessment, and therapeutic interventions. Orv Hetil. 2025; 166(47): 1843-1856.