Pharmacologically, genetically, or nutritionally, enhanced O‐GlcNAcylation was shown to promote cancer progression.[10] Notably, a recent study demonstrated that high levels of glucose promoted liver tumorigenesis through advanced glycosylation end‐product‐specific receptor (AGER)‐stimulated O‐GlcNAcylation of c‐Jun, indicating a crucial role of O‐GlcNAcylation in the development of HCC.[11] These results prompted us to propose dysregulation of O‐GlcNAc modification as a link connecting aberrant LRP1 expression to HCC pathogenesis. The gene discussed is LRP1; the disease is cancer.