Cathepsin L1 (CTSL) (CTSL)

Cathepsin L1 (CTSL) is a lysosomal cysteine protease belonging to the papain family, synthesized as an inactive zymogen known as pro-cathepsin L [UniProt P07711]. It plays a critical role in intracellular protein catabolism, antigen processing, and the activation of other pro-enzymes within the endolysosomal compartment [UniProt P07711, PubChem CTSL]. Beyond its physiological roles, CTSL is frequently overexpressed and secreted by cancer cells, where it facilitates extracellular matrix degradation, promoting tumor invasion and metastasis [PMID: 23541934]. Notably, CTSL has gained significant attention as a key host factor for viral entry, specifically by cleaving the spike proteins of viruses like SARS-CoV-2 and Ebola to facilitate membrane fusion [PMID: 32224931]. Therapeutic strategies targeting CTSL primarily involve small-molecule inhibitors designed to block its catalytic site, aiming to treat malignancies and viral infections [PMID: 23541934, PMID: 32224931]. However, achieving selectivity remains a challenge due to the structural similarity among various cathepsin family members, which can lead to off-target effects [PubChem CTSL]. Clinical interest in CTSL inhibitors has expanded from oncology to infectious diseases, particularly in the context of pandemic preparedness [PMID: 32224931]. Monitoring serum levels of CTSL has also been proposed as a biomarker for disease progression in both cancer and severe viral infections [PMID: 23541934, PMID: 32224931].

Other names

Cathepsin LPro-cathepsin LMajor excreted proteinMEPCTSL1

Cysteine protease inhibition to prevent the cleavage of substrate proteins, such as viral spike proteins or extracellular matrix components, thereby blocking viral entry or tumor metastasis [PMID: 23541934, PMID: 32224931].