From dynamic condensates to pathological assemblies: the phase behavior of tau and <i>α</i>-synuclein.

Neurons rely on precise protein folding, trafficking, and turnover to maintain synaptic function. Disruption of proteostasis(definition) promotes misfolded proteins that impair axonal transport, mitochondrial function, and signalling, contributing to neuronal loss. Although neurodegeneration has traditionally focused on stable amyloid deposits, many disease-associated proteins contain intrinsically disordered regions (IDRs) that can organize through liquid-liquid phase separation (LLPS). LLPS concentrates proteins and nucleic acids into dynamic condensates that regulate cellular processes, but these adaptive interactions can also promote condensate aging and less reversible, aggregation-prone states. Here, we review how sequence-encoded properties of tau and α-synuclein (α-syn) link physiological condensation to pathological protein assembly, while emphasizing that LLPS and amyloid formation are related but not obligatorily linked.