It is well documented that aberrant O‐GlcNAcylation leads to metabolic reprogramming, fueling cancer malignancies and promoting tumor progression.[24] OGA is the sole enzyme responsible for the removal of GlcNAc moieties from proteins and thus plays an important role in O‐GlcNAcylation and cancer metabolism.[25] Consistent with this, our results revealed that LRP1 deficiency was correlated with reduced OGA expression, concomitant with increased global O‐GlcNAcylation, O‐GlcNAcylated NF‐κB p65 levels, and nuclear NF‐κB p65 distribution in human HCCs. The gene discussed is NFKB1; the disease is cancer.