Together, these data underline the notion that hepatic TSC22D4 fulfils a critical and specific checkpoint function for the regulation of circulating VLDL-TG and hepatic TG load, and that high TSC22D4 levels induce serum TG depletion and hypobetalipoproteinemia under both normal and high caloric intake conditions. This evidence concerns the gene TSC22D4 and hypobetalipoproteinemia.