Epilepsy is a common neurological disorder characterized by hyperexcitability in the
brain. Its pathogenesis is classically associated with an imbalance of excitatory
and inhibitory neurons. Calretinin (CR) is one of the three major types of calcium-binding
proteins present in inhibitory GABAergic neurons. The functions of CR and its role
in neural excitability are still unknown. Recent data suggest that CR neurons have
diverse neurotransmitters, morphologies, distributions, and functions in different
brain regions across various species. Notably, CR neurons in the hippocampus, amygdala,
neocortex, and thalamus are extremely susceptible to excitotoxicity in the epileptic
brain, but the causal relationship is unknown. In this review, we focus on the heterogeneous
functions of CR neurons in different brain regions and their relationship with neural
excitability and epilepsy. Importantly, we provide perspectives on future investigations
of the role of CR neurons in epilepsy.
