GRN-gene

The GRN gene (Granulin Precursor) is a protein-coding gene located on chromosome 17q21.31. The gene codes for a protein called progranulin. This is an 88 kDa precursor protein (progranulin is also known as proepithelin and PC cell-derived growth factor). Cleavage of progranulin produces mature granulin in lysosomes, which can be further cleaved into a variety of active 6 kDa peptides. These smaller cleavage products are referred to as granulin A, granulin B, granulin C, etc. Epithelines 1 and 2 are synonymous with granulins A and B, respectively.

Progranulin is mainly localized in the membrane of lysosomes . Lysosomes are small specialized cell organelles that digest and recycle materials. The precursor progranulin is found in all tissues of the body, but is most active in cells that divide rapidly, such as skin cells (fibroblasts), cells of the immune system, and certain brain cells. Progranulin regulates the growth, division, and survival of these cells. However, various members of the granulin protein family can also act as inhibitors, stimulators, or have dual effects on cell growth.

Progranulin also plays an important role in early embryonic development, wound healing, and the body's immune response to injury (inflammation).

Progranulin is active in brain cells. However, little is known about the role of this protein in the brain. It appears to be crucial for the survival of nerve cells (neurons).

Diseases that are GRN-associated include:

• Ceroid Lipofuscinosis, Neuronal, 11 (CLN11) also named Neuronal Ceroid Lipofuscinosis 11.
• GRN-related frontotemporal lobar degeneration with Tdp43 inclusions

1. Cruts M et al. Loss of progranulin function in frontotemporal lobar degeneration. Trends Genet 24:186-194.
2. Eriksen JL et al (2008) Progranulin: normal function and role in neurodegeneration. J Neurochem. 104:287-297.
3. Huin V et al. (2020) Homozygous GRN mutations: new phenotypes and new insights into pathological and molecular mechanisms. Brain 143:303-319.
4. Le Ber I et al (2007) Progranulin null mutations in both sporadic and familial frontotemporal dementia. Hum Mutat 28:846-855.
5. Paushter DH et al. (2007) Phenotypic variability associated with progranulin haploinsufficiency in patients with the common 1477C-->T (Arg493X) mutation: an international initiative. Lancet Neurol 6:857-868.
6. Yu CE et al. (2010) The spectrum of mutations in progranulin: a collaborative study screening 545 cases of neurodegeneration. Arch Neurol 67:161-170.