May function in the control of the neuroendocrine secretory pathway. Proposed be a specific endogenous inhibitor of PCSK1 (PubMed:10632593, PubMed:10816562). ProSAAS and Big PEN-LEN, both containing the C-terminal inhibitory domain, but not the processed peptides reduce PCSK1 activity in the endoplasmic reticulum and Golgi. It reduces the activity of the 87 kDa form but not the autocatalytically derived 65 kDa form of PCSK1. Subsequent processing of proSAAS may eliminate the inhibition. Slows down convertase-mediated processing of proopiomelanocortin and proenkephalin. May control the intracellular timing of PCSK1 rather than its total level of activity (By similarity). Endogenous ligand for GPR171. Neuropeptide involved in the regulation of feeding. Endogenous ligand for GPR171. Neuropeptide involved in the regulation of feeding. Interacts via the C-terminal inhibitory domain with PCSK1 65 kDa form. Expressed in adult brain (all major structural regions), adrenal gland (medulla) and spinal cord (dorsal and ventral horn). Expressed in pancreatic islands. Expressed by E12.5 in essentially all differentiating neurons in the mantle layer of the myelencephalon, metencephalon, diencephalon, spinal cord and several sympathetic ganglia. During later stages of prenatal development, widespread expression continues in post-mitotic neurons of both the CNS and PNS and begins in endocrine cells of the anterior and intermediate pituitary. ProSAAS(1-180) increases secretion of enzymatically inactive PCSK1. The C-terminal inhibitory domain is involved in inhibition of PCSK1. It corresponds to the probable processing intermediate Big PEN-LEN, binds to PCSK1 in vitro and contains the hexapeptide L-L-R-V-K-R, which, as a synthetic peptide, is sufficient for PCSK1 inhibition. The four C-terminal amino acids of Big LEN are sufficient to bind and activate GPR171. Proteolytically cleaved in the Golgi. Big SAAS, Little SAAS, PEN and Big LEN are the major processed peptides in proSAAS-overexpressing PC-12 phaeochromocytoma cells (lacking PCSK1 and PCSK2 endopeptidases). Peptides corresponding to PEN and a proSAAS aa 40-59 have been detected in wild-type PC-12 cells.