Ctsl, short for Cathepsin L, encodes a lysosomal cysteine proteinase [2]. It plays a significant role in multiple physiological and pathological processes. For instance, it is involved in intracellular protein degradation [5], and has been associated with pathways related to cell homeostasis, as T cell-expressed Ctsl can process C3 into biologically active C3a and C3b, which is crucial for T cell survival and cytokine production [3].

Ctsl has been found to be highly expressed in many cancer tissues, such as glioblastoma multiforme (GBM), lung cancer, and gastric cancer. In GBM, higher Ctsl expression is linked to a lower survival rate, and its inhibitor can reduce GBM growth and induce apoptosis [1]. In lung cancer and glioma, high Ctsl expression is significantly correlated with a short overall survival, suggesting its role in the susceptibility to SARS-CoV-2 uptake and COVID-19 severity [2]. In gastric cancer, a high-risk subpopulation was identified based on Ctsl and ZBTB7B expressions, which showed unique tumor microenvironment features [4]. Additionally, in diabetes, hyperglycemia can induce Ctsl maturation, facilitating SARS-CoV-2 infection, and Ctsl has been implicated in diabetic complications like nephropathy and retinopathy [6].

In conclusion, Ctsl is a lysosomal cysteine proteinase with important functions in various biological processes and diseases. Its role in cancer, COVID-19 susceptibility, and diabetic comorbidities has been revealed through studies. Understanding Ctsl's functions through research models could potentially provide new therapeutic targets for these diseases.