Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disease selectively affecting motor neurons,leading to pro-gressive paralysis.Although most cases are sporadic,～10％ are familial.Similar proteins are found in aggregates in sporadic and familial ALS,and over the last decade,research has been focused on the underlying nature of this common pathology.Notably,TDP-43 inclusions are found in almost all ALS patients,while FUS inclusions have been reported in some familial ALS patients.Both TDP-43 and FUS possess 'low-complexity domains' (LCDs) and are considered as 'intrinsically disordered proteins',which form liquid droplets in vitro due to the weak interactions caused by the LCDs.Dysfunctional 'liquid-liquid phase separa-tion'(LLPS) emerged as a new mechanism linking ALS-related proteins to pathogenesis.Here,we review the current state of knowledge on ALS-related gene products associated with a proteinopathy and discuss their status as LLPS proteins.In addition,we highlight the therapeutic potential of targeting LLPS for treating ALS.