Given the essential involvement of lipid rafts and cholesterol in MAM composition—and the known cholesterol-binding property of σ2R (Jin et al., 2022), a comprehensive investigation into the potential convergence of σ1R and σ2R in regulating MAMs could reveal synergistic mechanisms and lead to more effective therapeutic strategies for neurodegenerative diseases. The gene discussed is TMEM97; the disease is neurodegenerative disease.