The most upstream of the different GNAS promoters with respect to the promoter of Gsα drives the expression of NESP55, a neuroendocrine secretory protein with an apparent molecular mass of 55,000 (Fig. 1). The NESP55 promoter is differentially methylated and active on the non-methylated maternal allele only [37, 52]. In humans, NESP55 protein is encoded by a single exon, while in mice, the ORF consists of two separate exons; however, in both species, these exons splice onto Gsα exons 2-13, which comprise the 3’ untranslated region (UTR) [37, 52]. The predicted molecular mass of NESP55 is 28 kDa, but it has the same electrophoretic mobility as a protein of 55 kDa [53]. NESP55 is a chromogranin-like protein expressed in neuroendocrine tissues, peripheral and central nervous system, and some endocrine tissues [53-56]. It is associated with the constitutive secretory pathway [57] and can be located in cholinergic, peptidergic, and adrenergic neurons [58]. In AtT20 cells, a corticotroph-like cell line, NESP55 has been shown to be exported out into the medium, a process which can be blocked markedly by lowering the temperature
