GPNMB

Glycoprotein nonmetastatic melanoma protein B (GPNMB), also known as osteoactivin or DC-HIL, is a transmembrane glycoprotein involved in tissue repair, immunomodulation, and tumor progression. It mediates cell-cell interactions through binding to integrins and CD44, modulating MAPK/ERK and PI3K/AKT signaling pathways. GPNMB is overexpressed in aggressive cancers including triple-negative breast cancer, glioblastoma, and melanoma, where it promotes metastasis, angiogenesis, and immune evasion by suppressing T-cell activation. Its dysregulation is also implicated in neurodegenerative disorders like Parkinson’s disease and inflammatory conditions such as atherosclerosis. Therapeutic strategies targeting GPNMB include antibody-drug conjugates (ADCs) like glembatumumab vedotin, which showed phase II efficacy in metastatic breast cancer but faced clinical setbacks. Emerging approaches involve bispecific antibodies and small-molecule inhibitors to disrupt its interaction with tumor-associated macrophages or downstream signaling.