en Cell, Stem Cell and Cancer Cell, Stem Cell and Cancer Review Review <div style="text-align: justify;"><span class="fontstyle0">The endoplasmic reticulum (ER) is an important organelle responsible for protein folding, calcium homeostasis and lipid biosynthesis. Accumulation of unfolded or misfolded proteins by hypoxia, loss of Ca</span><span class="fontstyle0" style="font-size:6pt;">2+ </span><span class="fontstyle0">homeostasis and nutrient deprivation leads to endoplasmic reticulum stress (ERS) and then the unfolded protein response (UPR) is activated as a defense mechanism to restore endoplasmic reticulum homeostasis. It is now known that the ERS and the UPR are implicated in a variety of diseases such as diabetes, inflammatory diseases, neurodegenerative diseases and osteoporosis. Steroid hormones such as 17-&beta;estradiol have been extensively reported to possess beneficial effects in different diseases. In this article, the concept of ERS, the underlying molecular mechanisms, and their relationship to several pathological conditions and finally, the role of 17-&beta;estradiol and its receptors in moderating ERS and UPR are discussed to provide theoretical basis for in-depth study.</span></div> Endoplasmic reticulum, 17 β-estradiol, Endoplasmic reticulum stress, Estrogen 226 238 http://ppj.phypha.ir/browse.php?a_code=A-11-1602-1&slc_lang=en&sid=1 Zeinab Farhadi 3200319475328460031277 3200319475328460031277 No Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Mansour Esmailidehaj 3200319475328460031278 3200319475328460031278 No Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Mohammad Ebrahim Rezvani 3200319475328460031279 3200319475328460031279 No Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Mohammad Shahbazian 3200319475328460031280 3200319475328460031280 No Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Faezeh Jafary-nezhad 3200319475328460031281 3200319475328460031281 No Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Mohammad Amin Ghafari 3200319475328460031282 3200319475328460031282 No Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Jalil Alizadehghalenoei 3200319475328460031283 3200319475328460031283 No Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Hossein Azizian H.Azizian@ssu.ac.ir 3200319475328460031284 3200319475328460031284 Yes Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran