Fig. 5. Disaggregases may reverse the irreversible transitions of disease-causing proteins that undergo LLPS. IDRs containing proteins in neurodegenerative diseases –tau in AD, α-syn in PD, RBPs (e.g., TDP43, FUS, and ANXA11) in ALS– can undergo LLPS. Differential interference contrast images show that ANXA11 undergoes a reversible LLPS to form liquid droplets, followed by an aberrant phase transition to form a fibrillar structure.⁶ Disaggregases to reverse the LLPS and aberrant phase transition of disease-causing proteins are a potential therapeutic target. AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; FUS, fused in sarcoma; IDR, intrinsically disordered region; PD, Parkinson’s disease; PTMs, posttranslational modifications; TDP-43, transactive response DNA-binding protein 43; TNPO1, transportin 1; KPNB1/KPNA2, karyopherin-β1/karyopherin-α2; bis-ANS, 4,4′-dianilino-1,1’-binaphthyl-5,5′-disulfonic acid; α-syn, α-synuclein.