After Alzheimer's disease, frontotemporal lobar degeneration (FTLD) is the second most common dementia-type in individuals under 65. Degeneration of neurons in the frontal cortex can give rise to changes in personality and to behavioral problems. When the temporal lobe is involved, disturbances in language occur, with problems in word retrieval and/or comprehension of words. The progressive course of this disorder is devastating for patients and their families.FTLD is a familial disease in 30-40% of patients. Recently, mutations in progranulin were discovered as a common cause underlying FTLD. Progranulin is a growth factor for epithelial cells, tumor cells and neurons. Most mutations in progranulin in FTLD patients result in reduced progranulin levels in the blood and the cerebrospinal fluid, suggesting that shortage of progranulin underlies the neurodegenerative process.Reduced levels of progranulin can also be found in family members of FTLD patients with progranulin mutations, if they carry the disease-causing mutation, even before the onset of symptoms. Our current understanding of this disease suggests that restoring normal progranulin levels in the central nervous system could be a therapy for/or prevent FTLD in patients with progranulin mutations.The aim of this project is to identify compounds that stimulate the expression of progranulin and can restore normal progranulin levels in patients with progranulin mutations. Thus, we hope to take the first steps towards a therapy for FTLD patients with progranulin mutations.