The loss of PINK1/Parkin-dependent mitochondrial clearance causes loss of dopaminergic neurons in the substantia nigra and contributes to the pathogenesis of Parkinson’s disease (PD).1 Several kinases were reported to regulate the ubiquitin E3 ligase activity of Parkin through phosphorylation but the involvement of protein tyrosine phosphatase (PTPase) for Parkin activity remains elusive.2 Although the roles of Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2) in development, hematopoiesis and cancer immunology have been intensively reported,3,4 knowledge of regulation and function of SHP2 in neuronal diseases remains scant. We previously showed that SHP2 maintains mitochondrial homeostasis through dephosphorylating ANT1 at Tyr-191 during NLRP3 inflammasome activation in macrophages.5 This previous study prompted us to investigate whether SHP2 regulates mitophagy and mitochondrial quality in neurons and, if so, whether targeting SHP2 could be a novel strategy for neuronal protection in PD.