Intrinsically disordered proteins (IDPs) are proteins that lack an ordered three-dimensional structure. Their discovery challenged the protein structure paradigm, that protein function depends on a fixed three-dimensional structure. This dogma has been challenged over the last decades showing that IDPs constitute one of the main types of proteins alongside globular, fibrous and membrane ones. IDPs cover a spectrum of states from fully unstructured to partially structured and include random coils, (pre-)molten globules, and large multi-domain proteins connected by flexible linkers.

IDPs are a very large and functionally important class of proteins. The flexibility of IDPs facilitates different conformational requirements for binding modifying enzymes as well as their receptors. IDPs are thus implicated in cell signaling, transcription, chromatin remodeling functions, helpers in ordered assembly of cellular machines, cellular regulation, organization and function as a central component of the control circuitry of the cell. Many diseases are associated to IDPs, their misfolding, formation of aggregated states or amyloid fibrils. Many of the proteins involved in diseases of protein misfolding are IDPs and as such are found in Alzheimer’s and Parkinson’s diseases, ALS, amylin, cardiomyopathies and neuropathies.