The balancing act of GABAergic synapse organizers

• The emerging inhibitory synapse organizers are concisely summarized.
• Various classes of inhibitory synapse organizers play roles at the synaptic, circuit, and systems levels.
• Dysfunctions of inhibitory synapse organizers underlie a subset of brain disorders.
• Inhibitory synapse organizers are crucial for maintaining the excitation-to-inhibition balance.

GABA (γ-aminobutyric acid) is the main neurotransmitter at inhibitory synapses in the mammalian brain. It is essential for maintaining the excitation and inhibition (E/I) ratio, whose imbalance underlies various brain diseases. Emerging information about inhibitory synapse organizers provides a novel molecular framework for understanding E/I balance at the synapse, circuit, and systems levels. This review highlights recent advances in deciphering these components of the inhibitory synapse and their roles in the development, transmission, and circuit properties of inhibitory synapses. We also discuss how their dysfunction may lead to a variety of brain disorders, suggesting new therapeutic strategies based on balancing the E/I ratio.