HSPA5 and obesity due to melanocortin 4 receptor deficiency: This paper focuses on the biological functions and roles of GRP78 in weight control and energy restriction via regulating mitochondrial autophagy and adenosine monophosphate-activated protein kinase-PPARγ coactivator 1α-sirtuin1 (AMPK-PGC1α-SIRT1) signal pathway (Figure 1, Pathway 1), revealing the subcellular mechanisms of GRP78 in the pathogenesis of obesity and providing new evidence for effective treatment of obesity and related diseases.