The axon initial segment in nervous system disease and injury

The axon initial segment (AIS), with its dense clusters of voltage‐gated ion channels decorating the axonal membrane, regulates action potential initiation and modulation. The AIS also functions as a barrier to maintain axodendritic polarity, and its precise axonal location contributes to the fine‐tuning of neuronal excitability. Therefore, it is not surprising that mutations in AIS‐related genes, disruption of the molecular organization of the AIS and altered AIS ion channel expression, function, location and/or density are emerging as key players in neurological disorders. Here, we consider the role of the AIS in nervous system disease and injury. The axon initial segment (AIS), with its dense clusters of voltage‐gated ion channels decorating the axonal membrane, regulates action potential initiation and modulation. The AIS also functions as a barrier to maintain axodendritic polarity, and its precise axonal location contributes to the fine‐tuning of neuronal excitability.