Selectively promotes the survival of dopaminergic neurons of the ventral mid-brain (PubMed:12794311). Modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra (By similarity). Enhances spontaneous, as well as evoked, GABAergic inhibitory postsynaptic currents in dopaminergic neurons (By similarity). Inhibits cell proliferation and endoplasmic reticulum (ER) stress-induced cell death (PubMed:18561914, PubMed:22637475, PubMed:29497057). Retained in the ER/sarcoplasmic reticulum (SR) through association with the endoplasmic reticulum chaperone protein HSPA5 under normal conditions (PubMed:22637475). Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia (PubMed:22637475). Following secretion by the ER/SR, directly binds to 3-O-sulfogalactosylceramide, a lipid sulfatide in the outer cell membrane of target cells (PubMed:29497057). Sulfatide binding promotes its cellular uptake by endocytosis, and is required for its role in alleviating ER stress and cell toxicity under hypoxic and ER stress conditions (PubMed:29497057). Interacts with HSPA5; the interaction is direct (PubMed:22637475). Component of a complex containing at least CRELD2, MANF, MATN3 and PDIA4 (By similarity). Retained in the endoplasmic reticulum (ER), and sarcoplasmic reticulum (SR) under normal conditions (PubMed:22637475). Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia (PubMed:22637475, PubMed:29497057). By endoplasmic reticulum stress (PubMed:18561914, PubMed:22637475, PubMed:29497057). By hypoxia (PubMed:29497057). The N-terminal region may be responsible for neurotrophic activity while the C-terminal region may play a role in the ER stress response. The N-terminal region may be required for lipid sulfatide binding. May contain sialic acid residues. Belongs to the ARMET family. Was originally (PubMed:8649854, PubMed:8971156 and PubMed:9174057) thought to be much longer and included an arginine-rich region thought to be the target of cancer-causing mutations. All these mutations are in what is now thought to be the 5'-UTR of the mRNA. It is uncertain whether Met-1 or Met-4 is the initiator. Extended N-terminus. Extended N-terminus. Extended N-terminus.