This review aims at delineating the contribution of several structural and functional partners of MAMs (i.e., Mitofusins (MFNs), Protein Kinase-like Endoplasmic Reticulum Kinase (PERK), the serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1α (IRE1α), and the sarco/endoplasmic reticulum Ca2+ ATPase 1 (SERCA) truncated isoform (S1T)), and MAMs complexes (i.e., IP3R-Grp75-VDAC, PACS2-PSS1, BAP31-FIS1-DRP1, VAPB-PTPIP51, and Sig-1R-Grp78) (Figure 2) in pathophysiological processes of AD. The gene discussed is HSPA5; the disease is Alzheimer disease.