GPNMB

Glycoprotein NMB (Osteoactivin)

Also known as: GPNMB, osteoactivin, DC-HIL, NMB

Biology & Mechanism

GPNMB is a lysosomal glycoprotein expressed on microglia that is upregulated in disease-associated and lipid-laden microglial states. GPNMB is co-regulated with progranulin (GRN) and both are involved in microglial lysosomal function. Elevated GPNMB has been observed in Parkinson's disease brain and in GBA1-related lipid storage contexts. GPNMB may be shed as a soluble form and could serve as a biomarker of microglial lysosomal stress.

Open Questions

  • What is the precise lysosomal function of GPNMB in microglia?
  • Can soluble GPNMB levels serve as a biomarker of microglial lysosomal stress in neurodegenerative diseases?
  • Is GPNMB upregulation a compensatory or pathological response in lipid-laden microglia?

Sources

Evidence Status

human tissuesingle-cell RNA-seqproteomicsanimal model

Disease Links

  • Parkinson's disease
  • Alzheimer's disease
  • Frontotemporal dementia

Related Targets

Last reviewed: June 1, 2026