The high differentiation and complexity of the human CM system make it more susceptible to the pathology of 43 kDa transactive response DNA-binding protein (TDP-43) pathology in ALS is typically detected in the motor cortex at early Braak stages, with sequential spread to the prefrontal cortex, thalamus, and hippocampus. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.