CALR as a Ca2+-binding chaperone located in ER lumen is responsible for modulating proper folding of neo-synthesized glycoproteins and for calcium retention [42, 43]; however, MANF as a negative regulator of unfolded protein response could alleviate hepatocellular carcinoma by suppressing EMT [44, 45]. Here, MANF is linked to hepatocellular carcinoma.