The interaction of proteins with lipid-raft localized receptors as a mechanism of regulating pathologic signaling has been observed for a number of neurodegenerative diseases, most notably in AD where soluble, stable amyloid-β dimers and trimers (Aβd/t) interact with the lipid raft-anchored cellular prion protein PrPC to stimulate a pathway mediated by activated NOX leading to the formation of rod-shaped bundles of filaments composed of a 1:1 complex of cofilin-actin [17–19]. Here, CFL1 is linked to neurodegenerative disease.