Figure 1.

CISD2 as a potential therapeutic drug target for the treatment of NAFLD and NASH, and the prevention of HCC. A, In mice, CDGSH iron sulfur domain 2 (Cisd2) haploinsufficiency impairs sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 2 isoform b (Serca2b) activity and disrupts Ca²⁺ homeostasis leading to non-alcoholic fatty liver disease (NAFLD). While obesity impairs Serca2b activity via a decrease in Serca2b protein level. B, In human, CISD2 and SERCA2b are both possible drug targets for the treatment of NAFLD and the prevention of hepatocellular carcinoma (HCC). In addition to directly target SERCA2b, CISD2 activators may have the potential to treat NAFLD indirectly by enhancing SERCA2b activity through an increase in CISD2 protein level. ER, endoplasmic reticulum; HBV, hepatitis B virus; HFD, high fat diet; NASH, nonalcoholic steatohepatitis.