Abstract. secretory granules in endocrine cells selectively store bioactive peptide hormones and amines, which are secreted in a regulated manner upon appropriate stimulation. in addition to bioactive substances, various proteins and lipids characteristic of secretory granules are likely recruited to a restricted space at the trans-Golgi network (TGn), and the space then matures to the secretory granule. Although experimental findings so far have strongly suggested that aggregation-and receptor-mediated processes are essential for the formation of secretory granules, the putative link between these two processes remains to be clarified. Recently, secretogranin III (SgIII) has been identified as a specific binding protein for chromogranin a (Cga), a representative constituent of the core aggregate within secretory granules, and it was later revealed that sgiii can also bind to the cholesterol-rich membrane domain at the TGn. based on its multifaceted binding properties, sgiii may act as a central player in the formation of cholesterol-rich membrane platforms. upon these platforms, essential processes for secretory granule biogenesis coordinately occur; that is, selective recruitment of prohormones, processing and modifying of prohormones, and condensation of mature hormones as an aggregate. This review summarizes the findings and theoretical concepts on the issue to date and then focuses on the putative role of SgIII in secretory granule biogenesis in endocrine cells.Key words: secretory granule, secretogranin iii, Cholesterol, sorting, secretory granule formation Secretory grAnuleS in endocrine cells are organelles that store bioactive peptides (peptide hormones and neuropeptides) and amines, which are exocytosed to the extracellular space in a calcium-dependent manner upon specific stimulation. Formation of secretory granules is initiated at the trans-Golgi network (TGn), and two processes have been emphasized for the sorting of soluble proteins to secretory granules, including aggregation-and receptor-mediated sorting processes [for reviews, see 1, 2].The importance of the aggregation-mediated sorting process in secretory granule biogenesis, first proposed by kelly [3], was evidenced by the experimental findings that granin proteins, such as chromogranin a (Cga), chromogranin b (Cgb), and secretogranin ii (sgii), could aggregate under conditions mimicking the intra-TGn milieu [4][5][6]. These aggregates significantly facilitate the condensation of bioactive peptides and amines, leading to the formation of secretory granules [4,7,8; for reviews see 9-13].even if aggregate formation at the TGn plays an important role in secretory granule formation, alternatively, certain soluble proteins might be recognized by the specific peripheral or transmembrane receptor molecules destined for the secretory granule. Membraneassociated carboxypeptidase e (CPe) was proposed by Loh and colleagues as a candidate for sorting receptor molecule based on the findings that proopiomelanocortin (PoMC) is mis-sorted to the constitutive...