Progranulin precursor (GRN)

Progranulin precursor (GRN) encodes progranulin, a secreted, glycosylated protein composed of multiple tandem granulin/epithelin domains. It functions mainly as a growth factor involved in numerous biological processes, including cell proliferation, migration, wound healing, inflammation modulation, and lysosomal integrity. Progranulin is widely expressed, particularly in proliferative and immune cells, and is essential for normal embryonic and neural development. In lysosomes, it is cleaved to yield smaller, bioactive granulin peptides with diverse regulatory roles; individual fragments may act as either cell growth stimulators or inhibitors. Genetic loss-of-function mutations in GRN are directly linked to certain neurodegenerative diseases, such as frontotemporal dementia (FTD2) and neuronal ceroid lipofuscinosis (CLN11). Conversely, increased expression is implicated in cancer progression, especially breast and brain tumors. Therapeutic targeting of progranulin is being explored but presents challenges due to its dual roles in tumorigenesis and neuroprotection.

Other names

ProgranulinParagranulinGranulin-1Granulin-2Granulin-3Granulin-4Granulin-5Granulin-6Granulin-7PGRNGP88Glycoprotein 88PCDGFPEPIPC cell-derived growth factorProepithelinCLN11AcrograninEpithelin precursorGlycoprotein of 88 kDaGranulin precursorGranulin FGranulin GEpithelin-2Granulin BEpithelin-1Granulin AGranulin CGranulin DGranulin Egranulin-epithelingranulinsproepithelin

Growth factor-like mitogenic and cell survival signaling (promotes proliferation, migration, wound repair); Lysosomal enzyme activity modulation (helps regulate trafficking and acidification, impacts protease activity); Anti-inflammatory modulation (blocks TNF-mediated neutrophil activation; preserves neuronal integrity)