Mesencephalic astrocyte-derived neurotrophic factor(MANF) is a secreted protein which belongs to the ARMET family. MANF selectively promotes the survival of dopaminergic neurons of the ventral mid-brain. It modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra. MANF enhances spontaneous, as well as evoked, GABAergic inhibitory postsynaptic currents in dopaminergic neurons. MANF inhibits cell proliferation and endoplasmic reticulum (ER) stress-induced cell death. The N-terminal region of ARMET may be responsible for neurotrophic activity while the C-terminal region may play a role in the ER stress response. MANF reduces endoplasmic reticulum (ER) stress and has neurotrophic effects on dopaminergic neurons. Intracortical delivery of recombinant MANF protein protects tissue from ischemic brain injury. MANF has been described as a survival factor for dopaminergic neurons. MANF and a homologous protein, the conserved dopamine neurotrophic factor (CDNF), form a novel evolutionary conserved family of neurotrophic factors. MANF expression was widespread in the nervous system and non-neuronal tissues.