MANF and Parkinson disease: Most uniquely, MANF possesses two modes of action: extracellularly, MANF potentially mediates signaling pathways, such as PKC signaling, through an unknown receptor [23], and administration of recombinant MANF protein is neuronal protective in a rat model of Parkinson’s disease [24]; intracellularly, MANF is abundantly expressed in the endoplasmic reticulum (ER), and functions as an ER-stress inducible protein [25, 26].