Mutations within the granulin (GRN) gene that encodes progranulin (PGRN) cause the neurodegenerative disease frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U). The receptor for PGRN in the CNS has not been previously identified. In this issue of Neuron, Hu and colleagues identify Sortilin (SORT1) as a key neuronal receptor for PGRN that facilitates its endocytosis and regulates PGRN levels in vitro and in vivo.
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