It was well established that S1R interacts with ionchannels and G-protein coupled receptors, thus exerting a chaperonerole in several neurological diseases as well as cancer progression.−, ,  The S2R is overexpressed in tumor cells and regulates their proliferativestatus; furthermore, S2R shows increasedexpression in neurons adjacent to Aβ oligomers in patients withAlzheimer’s disease (AD). Recently,S2R has been structurally identified as the transmembrane proteinof the endoplasmic reticulum (ER), that is, the cholesterol-responsiveNPC1-binding protein TMEM97. The gene discussed is TMEM97; the disease is cancer.