Thus, in individuals with NS and in Ptpn11 D61G NS mice, mutations result in increased ERK activation; in individuals with LS and in Ptpn11 Y279C LS mice, mutations results in loss of ERK activation and an increase in AKT activation; and in MSC SHP-2 KO mice, activation of both ERK and AKT is blocked. Here, AKT1 is linked to Leigh syndrome.