GPNMB (glycoprotein nmb) is a cell surface glycoprotein primarily expressed in macrophages and microglia with emerging roles in inflammation and neurodegeneration. Functionally, GPNMB mediates immune cell interactions through integrin and syndecan binding, regulates T cell activation and proliferation, and modulates cell migration and chemotaxis 1. GPNMB expression characterizes distinct tissue-resident and pro-inflammatory myeloid populations across multiple disease contexts. In hepatocellular carcinoma, GPNMB-expressing tumor-associated macrophages associate with poor prognosis 2. In fibrosis, GPNMB marks CD9+TREM2+ macrophages enriched at scarring edges that promote profibrotic collagen deposition through TGF-β1 signaling 3. Regarding clinical significance, GPNMB represents a Parkinson's disease risk gene (chromosome 7, rs199347); elevated plasma GPNMB correlates with PD severity and GPNMB mediates α-synuclein fibril internalization in neurons 4. GPNMB-high microglia subsets expand in Parkinson's disease, Alzheimer's disease, and multiple sclerosis, showing elevated pro-inflammatory markers including IL1B 56. In proliferative diabetic retinopathy, GPNMB+ microglia exhibit profibrotic properties and differentiate uniquely within the disease microenvironment 7. However, GPNMB's precise inflammatory role remains incompletely understood, with evidence supporting both pro- and anti-inflammatory functions 1.