This study gives evidence of the determinant role of CLR-M ATP6AP2 localization for neuronal and oligodendrocyte differentiation involving mechanisms of switches from Gαi/caveolin/canonical to Gαq/flotillin/PCP, the ERK/JNK pathway and Ca<sup>2+</sup>-dependent release of exosomes and as a potential target of drug therapy for neurodegenerative disorders.