Epilepsy is a common neurological disease affecting approximately 65 million people worldwide that manifests as spontaneous recurrent seizures (SRSs). Recently, it was reported that approximately 30% of patients with epilepsy have a poor response to antiseizure medications (ASMs) and ultimately progress to drug-resistant epilepsy (Alsfouk et al., 2019; Chen et al., 2018). Temporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy. Patients with TLE exhibit a high rate of ASM resistance and usually have cognitive disorders and mood disorders, which severely affect their quality of life. However, the underlying mechanism of TLE remains unclear and deserves further research and exploration (Bjorke et al., 2018; Pohlen et al., 2017).

Increasing evidence from previously published studies suggests that abnormal hippocampal synaptic transmission is closely related to the development or progression of TLE, in which synaptic regulatory proteins play a vital role (Santos et al., 2021). Synaptic regulatory proteins can regulate brain functions and contribute to epilepsy and TLE (Fels et al., 2021; Fukata and Fukata, 2017; Verhage and Sorensen, 2020). Sorbs2, a key synaptic regulatory protein, is highly expressed in the brain, especially in the hippocampus (Lee et al., 2016; Zhang et al., 2016). Sorbs2 is mainly distributed at excitatory postsynaptic sites and is coexpressed with postsynaptic density 95 (PSD95), which functions in regulating the growth and maturation of neuronal dendritic spines and excitatory synaptic transmission (Lee et al., 2016; Zhang et al., 2016). Although Sorbs2 is known as a synaptic regulatory protein that plays a crucial role in the regulation of hippocampal synaptic transmission, the expression pattern and potential regulatory roles of Sorbs2 in TLE remain unknown. Thus, in this study, we aimed to investigate the expression pattern of Sorbs2 in a kainic acid (KA)-induced TLE mouse model and in TLE patients to further determine whether Sorbs2 is involved in epileptogenesis or the development of TLE in this KA-induced TLE mouse model.