Determining how the distinct gene and protein profiles of various classes of neurons renders certain populations susceptible to TDP-43 pathology or specific post-translational TDP-43 modifications may assist in understanding the complex biology of TDP-43 in diseases such as ALS and FTD that are characterized by dramatic genetic, neuropathological and phenotypic heterogeneity (Simon et al., 2014), and elucidate protective molecular and cellular factors for therapeutic targeting. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.