In this study we investigated whether the presence of mutations in TMEM175 gene could reflect a characteristic lipidomic, metabolomic and proteomic signature of PD patients both at circulating and cellular levels.The study cohort included two groups of patients that differ for the presence of TMEM175 mutations, and a group of matched controls. We adopted an untargeted omics approach to disclose lipidomic, metabolomic and proteomic alterations in PD patients carrying TMEM175 mutations both in plasma and dermal fibroblasts.Integrated analysis of omics data revealed wide deregulation of lysosome, autophagy and mitochondrial pathways in PD patients carrying TMEM175 mutations, supporting a relevant role of this channel in regulating these cellular processes. The most significant altered lipid classes (CAR, Cer, FA, HexCer, PC, PC O-, SM, PI), and enzymes (PAG15, PP4P1, GALC, FYV1, PIGO, PGPS1, PLPP1) were involved in phosphosphingolipids and glycerophospholipids biosynthetic pathways. We also disclosed alterations of proteins involved in the insulin pathway (IGF2R), mitochondrial metabolism (ACD10, ACD11, ACADS) and autophagy (RAB7L). Interestingly, we also highlighted that the levels of CAR 18:2, HexCer 42:1;3O, and HexCer 42:2;3O, negatively correlated with age and age at onset (AAO) in PD patients. Strikingly, PI 34:1 was the only lipid showing a significant association with disease and a significant correlation (r=−0.5509; p=0.006) with age and earlier AAO of disease only in TMEM175 PD patients. Taken together our results highlight for the first time an association between circulating levels of a specific lipid specie and PD occurrence and AAO in presence of TMEM175 mutations.