To uncover the upstream signals that utilize E4BP4 to drive OPN overexpression in the context of NASH feeding, we transduced E4bp4‐LKO PMHs with Ad‐E4bp4 versus Ad‐GFP and treated the cells with a combination of lipotoxicity (palmitate at 300 μm) and pro‐inflammatory cytokine (IL‐11 at 5 ng mL−1). This evidence concerns the gene NFIL3 and metabolic dysfunction-associated steatohepatitis.