Adipocyte-specific SEL1L depletion promotes the aggregation and accumulation of LPL in the ER, leading to postprandial hypertriglyceridemia in mice.419 In the mouse liver, HRD1-mediated ERAD is constitutively active under basal conditions.417,420 HRD1 facilitates proteasomal degradation of the liver-specific ER-tethered transcription factor cAMP-responsive element-binding protein (CREBH) to downregulate fibroblast growth factor 21 (FGF21) expression. This evidence concerns the gene FGF21 and hypertriglyceridemia.