Progranulin, a secreted glycoprotein, is encoded in humans by the single GRN 
gene. Progranulin consists of seven and a half, tandemly repeated, non-identical 
copies of the 12 cysteine granulin motif. Many cellular processes and diseases 
are associated with this unique pleiotropic factor that include, but are not 
limited to, embryogenesis, tumorigenesis, inflammation, wound repair, 
neurodegeneration and lysosome function. Haploinsufficiency caused by autosomal 
dominant mutations within the GRN gene leads to frontotemporal lobar 
degeneration, a progressive neuronal atrophy that presents in patients as 
frontotemporal dementia. Frontotemporal dementia is an early onset form of 
dementia, distinct from Alzheimer's disease. The GRN-related form of 
frontotemporal lobar dementia is a proteinopathy characterized by the appearance 
of neuronal inclusions containing ubiquitinated and fragmented TDP-43 (encoded 
by TARDBP). The neurotrophic and neuro-immunomodulatory properties of 
progranulin have recently been reported but are still not well understood. Gene 
delivery of GRN in experimental models of Alzheimer's- and Parkinson's-like 
diseases inhibits phenotype progression. Here we review what is currently known 
concerning the molecular function and mechanism of action of progranulin in 
normal physiological and pathophysiological conditions in both in vitro and in 
vivo models. The potential therapeutic applications of progranulin in treating 
neurodegenerative diseases are highlighted.