Enzymes and structural proteins dominated thinking about protein structure and function
for most of the twentieth century. In recent decades, however, we have begun to appreciate the significant
physiological and pathological roles of nonglobular proteins. Amyloids first gained infamy
from their implications in a score of human mortal diseases. However, they have recently been discovered
to play vital physiological roles, such as memory consolidation in humans. This raises an
important question: Can we inhibit pathological amyloids without affecting functional amyloids?
Intrinsically disordered proteins (IDPs), many of which are prone to form amyloids, perform many
essential functions, yet their importance has only been recognized in the last quarter century. A subclass
of IDPs can form, under certain conditions, water immiscible liquid phases which serve to
process, regulate, store or transport RNA. Perturbation of these remarkable liquid phases can lead to
aggregates, such as those formed by the proteins TDP-43 and FUS, which are linked to ALS and
other dementia. Here, we summarize our changing view of intrinsically disordered, liquid phase
forming and amyloidogenic proteins and the uncertainties that will drive future research.