Compared with the paired adjacent normal liver tissues, concordant upregulation of Nogo-B, oxLDL, CD36, and CEBPβ and downregulation of p-YAP were detected in most NAFLD-associated HCC tissues, while there was no consistent expression pattern in HBV-associated HCC tissues, indicating that Nogo-B signaling was more activated in HCCs with metabolic disorders (Fig. 7a and Supplementary Fig. 7). Here, RTN4 is linked to metabolic dysfunction-associated steatotic liver disease.