We cannot eliminate the possibility that changes in AAK1 are consequences of the overall ALS pathology, nor can we disapprove that the regulatory function of AAK1 can be compromised earlier than the occurrence of its observable aggregated appearance which is not until symptomatic, consequently AAK1-invovled impairment in potentially regulating synaptic vesicle recycling and presynaptic function can be important in contributing to ALS pathology. The gene discussed is AAK1; the disease is amyotrophic lateral sclerosis.