**Background of GPNMB Antibodies**
GPNMB (Glycoprotein Non-Metastatic Melanoma Protein B), also known as HGFIN or DC-HIL, is a type I transmembrane protein encoded by the *GPNMB* gene. Structurally, it contains an extracellular domain with homology to pigment epithelium-derived factor, a single transmembrane region, and a short cytoplasmic tail. GPNMB is implicated in diverse cellular processes, including adhesion, differentiation, and signaling, often via interactions with integrins or other receptors. Its expression is upregulated in certain cancers, such as melanoma, glioblastoma, and breast cancer, where it exhibits dual roles—suppressing metastasis in melanoma but promoting tumor progression in other contexts through pro-inflammatory or pro-survival mechanisms.
GPNMB is also linked to non-cancer pathologies, including neurodegenerative diseases (e.g., ALS, Parkinson’s) and atherosclerosis, highlighting its role in inflammation and tissue repair. Antibodies targeting GPNMB serve as critical tools for research, enabling detection of its expression in tissues or cells. Therapeutically, GPNMB-directed antibody-drug conjugates (ADCs), like glembatumumab vedotin, have been explored to selectively deliver cytotoxic agents to GPNMB-overexpressing tumors. Other strategies include monoclonal antibodies to block pathogenic interactions (e.g., in autoimmune disorders) or CAR-T cell therapies.
While clinical trials for GPNMB-targeted ADCs show mixed outcomes, they underscore its potential as a biomarker and therapeutic target. Challenges remain in optimizing specificity, managing on-target toxicity, and understanding context-dependent roles of GPNMB in disease. Ongoing research aims to clarify its mechanistic contributions and refine therapeutic strategies.