May function in the control of the neuroendocrine secretory pathway. Proposed be a specific endogenous inhibitor of PCSK1. 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 66 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. Endogenous ligand for GPR171 (PubMed:24043826). Neuropeptide involved in the regulation of feeding (PubMed:24043826). Endogenous ligand for GPR171. Neuropeptide involved in the regulation of feeding. Interacts via the C-terminal inhibitory domain with PCSK1 66 kDa form. Expressed in brain (mostly hypothalamus and pituitary) and gut. Expressed in trigeminal ganglia and neuroendocrine cell lines. Expressed in pancreas, spinal cord and brain (most abundant in striatum, hippocampus, pons and medulla, and cortex) (at protein level). Broadly expressed from 9 dpc to 11 dpc, with some enrichment in neural tube-derived tissues. By 15 dpc, the expression is largely restricted to neuroendocrine tissues. 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. Little SAAS, PEN, PEN-20 and Big LEN are the major processed peptides in proSAAS-overexpressing AtT-20 pituitary corticotropic cell line.