Molecular and Functional Properties of Progranulin

We have identified progranulin (PGRN) gene as a sex steroid-inducible gene in the brain, which is involved in masculinization of the brain during the perinatal period and facilitation of adult neurogenesis in the hippocampus. PGRN was first reported in early 1990s by different groups as a protein containing seven and a half cysteine-rich granulin domains and having growth promoting properties involved in wound healing and tumorigenesis. Later it was found that mutations of the PGRN gene were associated with neurodegenerative and lysosomal storage diseases such as frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis, respectively. We have also found that PGRN is located in lysosomes and deficiency of PGRN results in exacerbated neuroinflammatory responses and increased lysosomal biogenesis in microglia after traumatic brain injury. It is now recognized that PGRN may regulate activities of lysosomal enzymes as a molecular chaperone and play a crucial role in maintaining cellular protein homeostasis. Deeper understanding of molecular and functional properties of PGRN would provide new insights for developing mechanism-based therapeutic approaches for multiple disorders including cancers and neurodegenerative diseases.