Delpino and Castelli (2002) showed that extracellular GRP78 are mostly derived from an active release from living cells and are not solely due to the protein leakage from dead cells. Recent studies have also demonstrated that GRP78 release is increased in cancer, obesity, or upon ER stress (Khadir et al., 2016; Steiner et al., 2017). Here, HSPA5 is linked to obesity due to melanocortin 4 receptor deficiency.