• YTHDF2 is upregulated in hepatic fibrosis and its inhibition reduces fibrosis, ROS, and iron levels in vivo and in vitro.
• YTHDF2 regulates ferroptosis in hepatic stellate cells by directly modulating ACSL4 expression in an m6A-dependent manner.
• Silencing ACSL4 blocks the pro-fibrotic and pro-ferroptotic effects of YTHDF2 overexpression, indicating a critical downstream mediator.
• Overexpression of ACSL4 reverses the anti-fibrotic effect of YTHDF2 knockdown, confirming the pathway's therapeutic relevance.