In Neuro2a cells and in motor cortex of patients with frontotemporal lobar degeneration with clinical features of motor neuron disease (FTLD-MND), Yamashita et al., 2012 showed that Calpain-1 and −2 are responsible for the calcium-mediated cleavage of TDP-43, leading to its toxic accumulation in the cytoplasm. The gene discussed is CAPN1; the disease is frontotemporal dementia.