This proposal involves the search for compounds for the treatment of Fronto-Temproal Dementia that increase the amount of a key neurpprotective molecule in the brains of FTD patients. Sortilin is involved in the degradation of Progranulin ("PGN"), an anti-inflammatory molecule whose mutation leads to familial FTD. Sortilin decreases extracellular concentrations of PGN, and thus decreases PGN's ability to act as a neuroprotective anti-inflammatory molecule protecting neurons against cell-death. The utility of compounds that selectively prevent the endocytosis and degradation of PGN by Sortilin as possible therapeutics for FTD has previously been proposed. This project proposal involves the development of assays using Sharp Edge Labs' proprietary screening platform to screen for compounds that can selectively inhibit Sortilin-dependent PGN endocytosis, without altering Sortilin's trafficking of other molecules important for neural survival and health (e.g. ApoE).