Frontotemporal Dementia (FTD) is an incurable neurodegenerative brain disease. Mutations in the granulin (GRN) gene are one of the most common causes of FTD. Pathogenic GRN mutations cause FTD by decreasing the amount and function of progranulin (PGRN). PGRN is a large 88 kDa protein that plays an important role in brain health. When PGRN levels are inadequate this ultimately leads to lysosome dysfunction, neuroinflammation, and death of neurons. Therefore, strategies to replace PGRN function are a logically approach to develop drugs to treat FTD caused by GRN mutations. Unfortunately, no PGRN replacement strategies are available to treat patients. This proposal is based on our novel discovery that a single granulin, a small peptide fragment of PGRN, is sufficient to rescue the full spectrum of neurodegenerative phenotypes in PGRN deficient mice, a model of FTD. We aim to translate this discovery into a peptide-based biologic that can enter the brain, replace PGRN function, correct disease phenotypes, and serve as a biotherapeutic drug to treat FTD and other disorders where PGRN is deficient.