Autophagy is an evolutionarily conserved pathway that delivers substrates to lysosomes for degradation.32 Moreover, intensive studies have shown that CTSB, as a notable lysosomal protease, is broadly upregulated in cancer and is essential for autophagic flux.33–35 Our data also implies CDK4 is a downstream substrate of CTSB in the autophagy process, as supported by our experiments in which selective knockdown of CTSB resulted in the partial reversal of CDK4 degradation. The gene discussed is CDK4; the disease is cancer.