Qu TT et al. (2021) reported that overexpression of MAS-related G-protein Coupled Receptor member D (MrgD) can inhibit ERS and fatty acid metabolism in HepG2 cells, suggesting the beneficial role of ERS to HCC. What’s worse, the HCC cells HepG2 and Hep3B under ERS could achieve immune escape by secreting HSP70-rich exosomes, activating the Toll-like receptor (TLR4) signaling pathway and promoting macrophage transformation to the M2 type (Hua W et al., 2021). Here, TLR4 is linked to hepatocellular carcinoma.