In conclusion, we provide evidence that the human APOA5 gene is a novel target of the liver-enriched endoplasmic reticulum-bound transcription factor and demonstrate that CREBH binds to the specific response element in the human APOA5 promoter and participates in the regulation of human APOA5 gene expression in human hepatoma cells. This evidence concerns the gene CREB3L3 and hepatocellular carcinoma.