Cathepsin B in programmed cell death machinery: mechanisms of execution and regulatory pathways

Cathepsin B (CatB), a cysteine protease, is primarily localized within subcellular endosomal and lysosomal compartments. It is involved in the turnover of intracellular and extracellular proteins. Interest is growing in CatB due to its diverse roles in physiological and pathological processes. In functional defective tissues, programmed cell death (PCD) is one of the regulable fundamental mechanisms mediated by CatB, including apoptosis, pyroptosis, ferroptosis, necroptosis, and autophagic cell death. However, CatB-mediated PCD is responsible for disease progression under pathological conditions. In this review, we provide an overview of the critical roles and regulatory pathways of CatB in different types of PCD, and discuss the possibility of CatB as an attractive target in multiple diseases. We also summarize current gaps in the understanding of the involvement of CatB in PCD to highlight future avenues for research.

Automated summary

Cathepsin B (CatB), a cysteine protease, is primarily located in the subcellular endosomal and lysosomal compartments and is involved in the degradation of intracellular and extracellular proteins. It plays diverse roles in physiological and pathological processes, including programmed cell death (PCD). However, CatB-mediated PCD can lead to disease progression under pathological conditions. This review provides an overview of the critical roles and regulatory pathways of CatB in different types of PCD, and discusses its potential as a therapeutic target in multiple diseases. Current gaps in understanding CatB's involvement in PCD are also highlighted to guide future research directions.