However, regardless of whether RNA metabolism, cytoskeletal dynamics, or proteostasis are perturbed in ALS, the most prominent pathology is the formation of proteinaceous aggregates in neurons and glial support cells composed of TDP-43, or SOD1, or FUS in a mutually exclusive manner (Farrawell et al., 2015). Here, TARDBP is linked to amyotrophic lateral sclerosis.