It can be divided into primary TDP-43 proteinopathies, referring to the disease driven primarily by TDP-43, which include FTLD-TDP, FTLD-ALS, for which TDP-43 is a pathological hallmark (Neumann et al., 2006; Kabashi et al., 2008; Sreedharan et al., 2008), and the Limbic-predominant Age-related TDP-43 Encephalopathy (LATE), which will be reviewed further later in this review. This evidence concerns the gene TARDBP and proteostasis deficiencies.