Neurodegenerative diseases such as Alzheimer's disease have proven resistant to 
new treatments. The complexity of neurodegenerative disease mechanisms can be 
highlighted by accumulating evidence for a role for a growth factor, progranulin 
(PGRN). PGRN is a glycoprotein encoded by the GRN/Grn gene with multiple 
cellular functions, including neurotrophic, anti-inflammatory and lysosome 
regulatory properties. Mutations in the GRN gene can lead to frontotemporal 
lobar degeneration (FTLD), a cause of dementia, and neuronal ceroid 
lipofuscinosis (NCL), a lysosomal storage disease. Both diseases are associated 
with loss of PGRN function resulting, amongst other features, in enhanced 
microglial neuroinflammation and lysosomal dysfunction. PGRN has also been 
implicated in Alzheimer's disease (AD). Unlike FTLD, increased expression of 
PGRN occurs in brains of human AD cases and AD model mice, particularly in 
activated microglia. How microglial PGRN might be involved in AD and other 
neurodegenerative diseases will be discussed. A unifying feature of PGRN in 
diseases might be its modulation of lysosomal function in neurons and microglia. 
Many experimental models have focused on consequences of PGRN gene deletion: 
however, possible outcomes of increasing PGRN on microglial inflammation and 
neurodegeneration will be discussed. We will also suggest directions for future 
studies on PGRN and microglia in relation to neurodegenerative diseases.