We and others previously reported that the expression level of SPRED2 is reduced in HCC [8,9] and that the loss of endogenous SPRED2 leads to increased EMT and stemness in HCC cells by activating ERK and its downstream signaling pathways [8], suggesting the importance of SPRED2-mediated regulation of the mitogen-activated protein kinase (MAPK)/ERK signaling in a variety of cellular processes in HCC cells. This evidence concerns the gene WNK2 and hepatocellular carcinoma.