Although subsequent results under dual gene modification of ENO2 and BNIP3 further validate and reveal the terminal target of ENO2, we still don’t understand why BNIP3-mediated mitophagy is specifically associated with ENO2 and importantly, how to connect with them in lenvatinib-resistant HCC cells (CCHuh7R/CCPLC-PRF-5R). The gene discussed is ENO2; the disease is hepatocellular carcinoma.