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To address this question, we experimentally determined the three-dimensional structure of TANGO2. Our crystallographic analysis indicates that interactions between heme and TANGO2 are nonspecific. Structural comparison of the TANGO2 crystal structure with known cysteine Ntn-hydrolases allowed us to identify a putative active site, catalytic residues and a substrate-binding cavity that correspond to residues that are mutated in pathogenic TANGO2 variants. Based on these features, we propose that TANGO2 may utilize fatty-acid derivatives as substrates, suggesting a potential role in lipid metabolism. Mutations in the human TANGO2 gene cause TANGO2 deficiency disorder, a multisystem, life-threatening disease with onset in early childhood. 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