In addition to numerous physiological roles of PARylation that range from gene expression to DNA repair, mitochondrial biogenesis, neuroinflammation, and regulation of a variety of signaling pathways inducing different forms of cell death, alterations in this PTM were associated with aberrant LLPTs and pathological aggregation of several proteins, such as α-synuclein, TDP-43, and heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) [146] associated with Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington disease (HD), and amyotrophic lateral sclerosis (ALS). This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.