Thiol protease important for the overall degradation of proteins in lysosomes (Probable). Involved in the solubilization of cross-linked TG/thyroglobulin and in the subsequent release of thyroid hormone thyroxine (T4) by limited proteolysis of TG/thyroglobulin in the thyroid follicle lumen (PubMed:12782676). In neuroendocrine chromaffin cells secretory vesicles, catalyzes the prohormone proenkephalin processing to the active enkephalin peptide neurotransmitter (PubMed:12869695). In thymus, regulates CD4(+) T cell positive selection by generating the major histocompatibility complex class II (MHCII) bound peptide ligands presented by cortical thymic epithelial cells (PubMed:12021314). Also mediates invariant chain processing in cortical thymic epithelial cells (PubMed:9545226). Major elastin-degrading enzyme at neutral pH. Accumulates as a mature and active enzyme in the extracellular space of antigen presenting cells (APCs) to regulate degradation of the extracellular matrix in the course of inflammation (PubMed:12417635). Secreted form generates endostatin from COL18A1 (PubMed:10716919). Critical for cardiac morphology and function (PubMed:11972068). Plays an important role in hair follicle morphogenesis and cycling, as well as epidermal differentiation (PubMed:12163394). Required for maximal stimulation of steroidogenesis by TIMP1 (By similarity). Specificity close to that of papain. As compared to cathepsin B, cathepsin L exhibits higher activity toward protein substrates, but has little activity on Z-Arg-Arg-NHMec, and no peptidyl-dipeptidase activity. Long isoform of CD74/Ii chain stabilizes the conformation of mature CTSL by binding to its active site and serving as a chaperone to help maintain a pool of mature enzyme in endocytic compartments and extracellular space of APCs (PubMed:11483509, PubMed:12417635). IFNG enhances the conversion into the CTSL mature and active form (PubMed:11483509). Inhibited by CST6. Inhibited by the glycopeptide antibiotic teicoplanin. Inhibited by amantadine (By similarity). Optimum pH is 5.5. Dimer of a heavy and a light chain linked by disulfide bonds (Probable). Interacts with Long isoform of CD74/Ii chain; the interaction stabilizes the conformation of mature CTSL (PubMed:11483509, PubMed:12417635). Localizes to the apical membrane of thyroid epithelial cells. Released at extracellular space by activated dendritic cells and macrophages (PubMed:12417635). Expressed in thymus, kidney and liver (PubMed:9545226). Expressed in thyroid epithelial cells. Expressed in cortical thymic epithelial cells (PubMed:9545226). Expressed by antigen presenting cells (APCs) such as dendritic cells and macrophages (PubMed:11483509, PubMed:12417635). During export along the endocytic pathway, pro-CTSL undergoes several proteolytic cleavages to generate the CTSL single-chain and two-chain mature forms, composed of a heavy chain linked to a light chain by disulfide bonds (PubMed:11483509). Autocleavage; produces the single-chain CTSL after cleavage of the propeptide. The cleavage can be intermolecular (By similarity). Enlarged thyroid follicles, reduced extension of the thyroid epithelium and increased levels of Tg/thyroglobulin in the thyroid follicles. Lysosomes are enlarged and CTSB/cathepsin B is mis-localized to the apical membrane of thyroid epithelial cells. Serum levels of thyroid hormone thyroxine (T4) are reduced. The phenotype is more severe in CTSK/cathepsin K and CTSL double knockout mice (PubMed:12782676). Mutants possess reduced levels of Met-enkephalin in brain (PubMed:12869695). Mice show impaired CD4(+) T cell selection (PubMed:12021314). They have reduced numbers of CD4(+) T cells in the thymus and periphery and CD8(+) T cells relatively increased (PubMed:9545226). One-year-old mutant mice show ventricular and atrial enlargement associated with a comparatively small increase in relative heart weight and severely impaired myocardial contraction. They show interstitial fibrosis and pleomorphic nuclei (PubMed:11972068). Cardiomyocytes contain multiple large and apparently fused lysosomes characterized by storage of electron-dense heterogeneous material (PubMed:11972068). Mutants have delayed hair follicle morphogenesis and late onset of the first catagen stage. Their skin show mild epidermal hyperplasia and hyperkeratosis, severe hyperplasia of the sebaceous glands, and structural alterations of hair follicles (PubMed:12163394). Belongs to the peptidase C1 family.