GRN encodes progranulin (PGRN), a secreted lysosomal protein with critical roles in cellular homeostasis and neuronal survival. PGRN functions as a pH-dependent interactor with bis(monoacylglycero)phosphate (BMP), an endolysosomal phospholipid that enhances lysosomal proteolysis and lipolysis 1. The protein maintains ganglioside catabolism by supporting BMP levels in lysosomes, with PGRN deficiency leading to ganglioside accumulation 2. PGRN is transported to lysosomes through sortilin receptor-mediated shuttling, where it undergoes cleavage to produce functional granulin polypeptides 3. Beyond lysosomal function, PGRN serves as an immune regulator, particularly in regulatory T cells where it supports bone repair through CCR8+ Treg signaling 4. Heterozygous GRN loss-of-function mutations cause frontotemporal dementia (FTD-GRN) through haploinsufficiency, resulting in TDP-43 inclusions, neuroinflammation, and blood-brain barrier dysfunction 5. FTD-GRN patients exhibit neurovascular dysfunction with perturbed endothelial cells and reduced pericyte coverage 5. Therapeutic approaches targeting PGRN restoration through gene therapy or sortilin inhibition show promise in preclinical and early clinical studies 63. The protein's diverse functions in lysosomal homeostasis, immune regulation, and neuronal survival make it a critical factor in neurodegeneration prevention.