Cathepsin L, V, K, and H are lysosomal cysteine proteases belonging to the papain-like enzyme family, primarily involved in protein degradation, antigen processing, and tissue remodeling. Antibodies targeting these enzymes are widely used to study their expression, localization, and function in physiological and pathological contexts. Cathepsin L (CTSL) regulates extracellular matrix degradation, antigen presentation, and viral entry, with its antibodies applied in cancer metastasis and neurodegenerative disease research. Cathepsin V (CTSV, also called Cathepsin L2) shares structural homology with CTSL but exhibits tissue-specific roles, such as thymic selection; its antibodies help explore immune regulation and corneal homeostasis. Cathepsin K (CTSK) is a key osteoclast protease essential for bone resorption, making CTSK antibodies critical in osteoporosis and bone metastasis studies. Cathepsin H (CTSH) functions in protein processing and epidermal differentiation, with antibodies used to investigate skin disorders and tumor progression. These antibodies are commonly validated in techniques like Western blotting, immunohistochemistry, and immunofluorescence. However, cross-reactivity between homologous family members (e.g., CTSL and CTSV) requires careful validation. Dysregulation of these proteases is linked to cancer, autoimmune diseases, and lysosomal storage disorders, driving demand for specific antibodies in diagnostic and therapeutic research.