CTSB and cancer: 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.