OPTN and amyotrophic lateral sclerosis: It is worth noting that another functional category of ALS–FTD-causing genes, other than RBPs, is PQC, including VCP, SQSTM1, OPTN, and UBQLN2. Among them, de-mixing of SQSTM1 and UBQLN2 in both cell-free and cellular systems were identified and mutations linked to ALS–FTD lead to reduced fluidity (SQSTOM1) and even liquid-to-solid phase transition (UBQLN2) (Dao et al., 2019; Faruk et al., 2021).