We revealed extensive disease-dependent transcriptional regulatory network rewiring, characterized by altered expression and motif enrichment of key TFs implicated in MASLD pathogenesis, including FOXO3, MLXIPL, PROX1, PPAR, HNF1B/4A, and TEAD1 (Extended Data Fig. 4J-K). Here, PROX1 is linked to metabolic dysfunction-associated steatotic liver disease.