Progranulin: A Key Target in Inflammation, Proteostasis, and Neurodegeneration

Progranulin (GRN) is a multifunctional protein with growing significance in neuroscience and immunology. As a secreted glycoprotein, it plays central roles in inflammation, tissue repair, lysosomal function, and neuroprotection, making it a valuable target for researchers studying complex diseases like frontotemporal dementia (FTD), Alzheimer’s, and Parkinson’s.

At Aviva, we’ve developed a suite of high-performance tools to help scientists investigate progranulin biology with precision and flexibility. These include five new anti-progranulin monoclonal clones validated for ELISA, Western blot, and immunocytochemistry, a knockout-validated polyclonal antibody, and customizable Protein On Demand™ options for recombinant proteins and assay development.

Structure and Function

Progranulin is secreted by a wide range of cell types, including neurons and microglia in the central nervous system as well as immune and epithelial cells in the periphery. Once produced, the full-length 88 kDa precursor protein can be cleaved into smaller peptides known as granulins.

In the brain, progranulin helps regulate microglial activity and supports lysosomal function, both of which are critical for maintaining cellular homeostasis and responding to injury. Its involvement in wound healing, immune signaling, and cell survival further underscores its importance across systems.

Progranulin and Neurodegenerative Disease

The connection between progranulin and neurodegenerative diseases is pretty well established at this point. Inherited mutations in the GRN gene (often leading to haploinsufficiency) are a major genetic cause of frontotemporal dementia (FTD). In these cases, reduced progranulin expression disrupts lysosomal pathways and heightens neuroinflammatory responses.

But that's not all. Progranulin deficiency is increasingly recognized as a contributing factor in other diseases where lysosomal dysfunction and chronic inflammation are involved, including Alzheimer’s, Parkinson’s, and ALS. Lower progranulin levels can tip the balance toward pathological protein accumulation, impaired waste clearance, and microglial dysregulation.

A Therapeutic Target with Growing Potential

With its central role in maintaining neuronal health and regulating immune activity, progranulin is being actively explored as a therapeutic target. Restoring progranulin levels holds promise for slowing or reversing disease progression, and this can be accomplished by either by upregulating endogenous expression or delivering exogenous protein.

One of the most promising approaches is AAV-based gene therapy, which uses adeno-associated viruses to deliver functional GRN genes directly to affected brain regions. Preclinical studies published in Nature and other journals have shown encouraging results, pointing toward a viable path for treating GRN-linked FTD and potentially other conditions.

See the study: Progranulin AAV gene therapy for frontotemporal dementia: translational studies and phase 1/2 trial interim results 

Read a review: Progranulin as a therapeutic target in neurodegenerative diseases

Tools for Progranulin Research: To support scientists working across neurology, inflammation, and diagnostics, Aviva has launched five new anti-progranulin recombinant monoclonal antibody clones. Each has been carefully designed and validated for high specificity and sensitivity in multiple applications, with kinetics data available. These tools provide researchers with greater flexibility to match the right clone to their specific application or assay format. While an older technology, we also offer a knockout-validated polyclonal antibody known for its robust performance across applications.

Explore our GRN portfolio today or get in touch with our technical team to discuss your project needs.

AND STAY TUNED:

At this year’s Alzheimer's Association International Conference (AAIC), April Livengood will be presenting a new poster featuring a case study on generating high-affinity recombinant monoclonal antibodies to progranulin using our discovery and screening platform. Stay tuned to see how these clones were selected for performance across multiple applications. If you’d like to receive a copy of this poster after the conference, please submit the for below. Thanks for your interest!