The Molecular Structure, Expression, and Emerging Role of the 15-Leucine-Rich Repeat Containing Membrane Protein (LRRC15) in Skeletal Biology and Diseases

The 15-leucine-rich repeat containing membrane protein (LRRC15) is a transmembrane protein derived from the leucine-rich repeat (LRR) superfamily that participates in various cell-cell and cell-extracellular matrix interactions, regulating fibrogenesis, vascular invasion, tumorigenesis, and the formation of the innate immune barrier to drive specific antiviral responses. LRRC15, whose expression is reportedly induced by TGF-β and IL-1β stimulation, was recently found to be associated with the development of skeletal diseases, and its presence has been related to the pathophysiological processes of osteoporosis, osteoarthritis and rheumatoid arthritis. Various transmembrane and intracellular signaling transductions are involved in LRRC15-mediated molecular functions, including integrin, NF-κB, Wnt/β-catenin, etc. Additionally, LRRC15 is considered a novel mesenchymal protein and an important biomarker for the occurrence and development of osteosarcoma. Understanding the role of LRRC15 in the bone, joint and tumor microenvironment will facilitate the development of new therapeutic options-particularly LRRC15-based target therapies-for skeletal diseases.