CTSL encodes cathepsin L, a lysosomal cysteine protease with diverse cellular functions. The enzyme primarily functions in proteolytic processing, including cleavage of the CUX1 transcription factor to regulate cell cycle progression 1. CTSL demonstrates broad substrate specificity, processing complement component C3 into biologically active C3a and C3b fragments that support T cell homeostasis and effector differentiation 2. The protease also facilitates viral entry, particularly for SARS-CoV-2, by cleaving spike proteins to enable membrane fusion during endosomal entry 3. CTSL expression is elevated in various cancers including glioblastoma, gastric cancer, and lung cancer, where high expression correlates with poor overall survival 45. In the tumor microenvironment, macrophage-derived CTSL promotes epithelial-mesenchymal transition and cancer cell migration and metastasis 6. The enzyme's upregulation in cancer tissues may increase susceptibility to SARS-CoV-2 infection, as CTSL expression is significantly higher than ACE2 in both normal and malignant lung tissues 5. Therapeutically, CTSL inhibition shows promise for both cancer treatment and antiviral therapy, with compounds like cordycepin and UNC0638 effectively reducing CTSL activity 53.