Moreover, deregulated Ca2+ levels can activate the Ca2+-dependent calpain protease that cleaves TDP-43 at the C-terminal, generating aggregation prone N-terminal segments that are found misallocated in the majority of ALS patients (even in those that do not carry TDP-43 mutations associated with ALS10) driving TDP-43 toxicity across ALS pathology (Aggad et al., 2014; Yamashita and Kwak, 2014). The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.