Last reviewed: June 1, 2026

2017Molecular Neurodegeneration

Lysosomal processing of progranulin

Zhou X, Paushter DH, Feng T, Sun L, et al.

Abstract summary

Showed that progranulin localizes to lysosomes in microglia and regulates lysosomal cathepsin activity and pH. GRN-deficient microglia have enlarged lysosomes with aberrant cathepsin levels. This lysosomal dysfunction phenotype can be rescued by progranulin supplementation, the basis for recombinant GRN therapy approaches.

Evidence labels

in vitro assayanimal modelhuman tissue

Targets

Diseases

  • Frontotemporal dementia

Species

mouse, human

Methods

cell biology, organelle fractionation, live imaging

Therapeutic relevance

Establishes the lysosomal GRN pathway as the direct therapeutic target for progranulin replacement in FTD.

Last reviewed: June 1, 2026