Progranulin

Progranulin (GRN, P28799) is a secreted 63 kDa protein that functions as a key regulator of lysosomal homeostasis and a pleiotropic growth factor. It promotes protein trafficking to lysosomes, enhances lysosomal acidification, facilitates enzymatic degradation pathways, and modulates inflammation and neuronal survival through effects on axonal outgrowth and neuronal integrity (UniProt: P28799).

The protein is expressed broadly and plays roles in wound healing, cell proliferation, and immune regulation. It is clinically associated with frontotemporal dementia type 2 (FTD2, MIM 607485) and neuronal ceroid lipofuscinosis type 11 (CLN11, MIM 714706), both progressive neurodegenerative conditions involving lysosomal dysfunction (UniProt: P28799).

In Alzheimer's disease, progranulin shows significantly increased abundance in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of +0.451 across the TMT-labeled subcellular fractions analyzed (Chaparral AD proteomics). This upregulation suggests a potential compensatory or pathologically relevant response in the AD brain microenvironment.