Functional membrane trafficking is critical for many aspects of neuronal growth and differentiation and the regulation of the balance between endocytosis and recycling has been postulated to create polarized membrane flow during cell surface remodelling. In this context, a neuronal membrane glycoprotein M6a (Gpm6a) from the PLP/DM20 family of proteolipid proteins has drawn our attention. Gpm6a is a four-transmembane-domain protein abundantly expressed in neurons of the central nervous system. It functions in different processes of neuronal development and its overexpression leads to the extensive formation of filopodia. The endocytic and recycling pathway of Gpm6a has been shown to affect the formation and maintenance of synapses in neurons. But the mechanisms by which Gpm6a is targeted for recycling or degradation are still unknown. Here, we demonstrate that the overexpression of a mutant form of Gpm6a, E258A, decreases filopodium formation and the complexity of neuronal arborization in rat hippocampal neurons. At the same time, increases dynamics of Gpm6a vesicles and redirects intracellular trafficking of Gpm6a towards late endosomal/ lysosomal compartments increasing its colocalization with Rab 7 and Lamp1-positive compartments. We propose E258 residue as a critical switch that regulates Gpm6a targeting for recycling or degradation and by this way contributes to neuronal morphogenesis.