Two recent reviews have highlighted the pleiotropic mechanism of actions of σ1R/σ2R ligands, including modulation of cellular stress and excitotoxicity, which have shown benefits in conditions such as stroke, epilepsy, neuropathic pain, and psychiatric disorders (Piechal et al., 2021; Drewes et al., 2025; Ruiz-Cantero et al., 2024). This evidence concerns the gene TMEM97 and epilepsy.