The interactions between tumor cells and bone promote the production of angiogenic and bone resorbing factors by tumor, and further enhance tumor growth in bone.476 Of note, the bone microenvironment houses abundant growth factors including TGF-β, IGF-1, and -2, FGFs, PDGFs and BMPs.477 During tumor-induced osteoclastic bone resorption, these factors are released and enriched in the bone microenvironment. Here, CLN5 is linked to neoplasm.