Therapeutic targeting of AREL1 in hepatic stellate cells attenuates MASH-related liver fibrosis

Nature Communications, Published online: 21 June 2026; doi:10.1038/s41467-026-74481-3 Hepatic stellate cell (HSC) activation drives liver fibrosis. Here, the authors show that apoptosis-resistant E3 ubiquitin protein ligase 1 (AREL1) is upregulated in HSCs of patients with metabolic-associated steatohepatitis (MASH) and promotes fibrosis via the ILK–PI3K–AKT pathway. Targeting AREL1 with vitamin A-modified lipid nanoparticles (LNPs) reduces MASH-associated fibrosis in male mice.