Progranulin: at the interface of neurodegenerative and metabolic diseases

• Progranulin is a secreted glycoprotein found in plasma and CSF.
• Progranulin has growth factor-like and inflammation-related properties.
• Progranulin deficiency causes a neurodegenerative disease – frontotemporal dementia.
• Obese and type 2 diabetic individuals have increased serum progranulin levels.
• Grn−/− mice are protected from diet-induced obesity and insulin resistance.

Progranulin is a widely expressed, cysteine-rich, secreted glycoprotein originally discovered for its growth factor-like properties. Its subsequent identification as a causative gene for frontotemporal dementia (FTD), a devastating early-onset neurodegenerative disease, has catalyzed a surge of new discoveries about progranulin function in the brain. More recently, progranulin was recognized as an adipokine involved in diet-induced obesity and insulin resistance, revealing its metabolic function. We review here progranulin biology in both neurodegenerative and metabolic diseases. In particular, we highlight the growth factor-like, trophic, and anti-inflammatory properties of progranulin as potential unifying themes in these seemingly divergent conditions. We also discuss potential therapeutic options for raising progranulin levels to treat progranulin-deficient FTD, as well as the possible consequences of such treatment.