Emerging trophic activities of mesencephalic astrocyte-derived neurotrophic factor in tissue repair and regeneration

•MANF is a soluble endoplasmic reticulum (ER) luminal protein.•MANF plays a critical role in immune regulation and associated signaling pathways.•MANF promotes cell survival and tissue repair in pathological states. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a soluble endoplasmic reticulum (ER) luminal protein and its expression and secretion can be induced by ER stress. Despite initially being classified as a neurotrophic factor, MANF has been demonstrated to have restorative and protective effects in many different cell types such as neurons, liver cells, retinal cells, cardiac myocytes, and pancreatic β cells. However, underlying molecular mechanisms are complex and remain incompletely understood. The aims of this review are to highlight the latest advances in the understanding of the trophic activities of MANF in tissue repair and regeneration as well as underlying molecular mechanisms. The structural motifs and immune modulation of MANF are also described. We therefore propose that MANF might be a promising therapeutic target for tissue repair.