PSMD14 can reduce K63‐linked polyubiquitin chain on PKM2 to decrease the ratio of tetrameric PKM2 without altering the expression level of PKM2 protein, thereby attenuating PK activity to induce Warburg effect and promoting PKM2 nuclear translocation to upregulate transcription of downstream cancer‐promoting genes. The gene discussed is PSMD14; the disease is cancer.