A substantial body of evidence suggests that S1R, in combination with BIP, a regulator of endoplasmic reticulum stress (ERS), plays a pivotal role in the ERS pathway, which is a component of cellular stress and a core mechanism underlying synaptic loss and neurodegeneration in AD pathology (Ortega-Roldan et al., 2013; Venkataraman et al., 2022). Here, TMBIM4 is linked to Alzheimer disease.