lysosomal resident protein and sortilin and lipoprotein receptor-related protein 1 (LRP1) have been demonstrated to be the lysosomal trafficking receptors for PGRN with the help of Prosaposin. In the brain, PGRN is primarily expressed in mature neurons and microglia. Absence of progranulin in microglia causes increased production and release of multiple cytokines, suggesting that PGRN regulates microglia activation. PGRN seems to affect microglial proliferation, recruitment, differentiation, activation and phagocytosis, suggesting that PGRN plays a central role in the regulation of neuroinflammatory responses. In neurons, PGRN i) co-localizes in late endosomes and early lysosomes with the transmembrane protein TMEM106B, ii) co-localizes with markers such as BDNF along axons, iii) influences synaptic structure and function at synaptic and extra-synaptic sites, where it is secreted in an activity-dependent manner, and iv) extracellular PGRN is endocytosed and delivered to lysosomes. The lysosomal function of PGRN is not well characterized, but probably involves regulation of proteins such as cathepsins, glucocerebrosidase (GBA) or TMEM106B and likely contributes to neurodegeneration.

Progranulin expression in plasma predicts GRN mutations status, independently of symptom onset proximity. Progranulin loss-of-function mutations are among the most frequent genetic causes, responsible for 20% of familial FTLD. If a patient carries a mutation in the progranulin gene, it can be detected using AdipoGen's Progranulin (human) ELISA Kits. These are the only and unique kits on the market detecting all mutations of Progranulin [4]. See below an overview of our Unique ELISA Kits, Proteins and Antibodies, related to Progranulin and its receptor Sortilin.