• Resident CD24+LCN2+ LPCs are significantly enriched in NASH patients and contribute to fibrosis progression.
• LPCs interact with proinflammatory macrophage subtypes, particularly MP-2, which shows NF-κB pathway hyperactivation.
• The study identifies COL10A1 and TPPP3 as novel markers of the proinflammatory macrophage subtype associated with fibrosis.
• These findings provide potential therapeutic targets for NASH by modulating LPC-macrophage crosstalk.