The cellular and developmental basis of autism spectrum disorder (ASD) still represents a significant gap in our knowledge of this developmental disorder. To understand how ASD affects brain development, comprehensive disease models are needed. Such models will yield insight into the developmental programs that are affected in ASD and how these perturbations ultimately affect behavioral output.

Imbalances in excitatory versus inhibitory postsynaptic signaling in the central nervous system (CNS) have been associated with autism spectrum disorders (ASD). These imbalances are caused by mis-regulated chloride (Cl-) concentrations in the CNS. The potassium-chloride co-transporter is the key player involved in maintaining the low Cl- concentrations in neurons necessary for proper signaling. KCC2 is thus a potential target for therapeutic strategies aimed at rescuing excitatory/inhibitory imbalances in ASD and other disorders affected by such imbalances. However, targeted therapeutic strategies require detailed knowledge of the drug targets, and currently, there is insufficient biochemical information to target KCC2 using rational approaches.