However, knockout phenotypes cannot be fully rectified by treatment of the OPN-knockout mice or cells with recombinant OPN, and antibody neutralization of OPN in the wild-type mice or cells did not reproduce knockout phenotypes.9 In our previous work, recombinant human OPN (rhOPN) did not fully compensate for the weakened metastatic ability of HCC cells by OPN interference.10 Researchers gradually recognized that intracellular OPN (iOPN) existed and functioned separately from sOPN. The gene discussed is SPP1; the disease is hepatocellular carcinoma.