Polypeptides comprising an amino acid sequence of Slc26a6 or IRBIT comprising a mutation that increases NaDC-1 binding, stability of the polypeptide, stability of NaDC-1 complex or a combination thereof are provided. Polypeptides comprising an amino acid sequence of a mutant succinate receptor 1 (mutSUCNR1), comprising a mutation that increases succinate binding, stability of the polypeptide, stability of the mutSUCNR1-succinate complex or combinations thereof are also provided. Compositions comprising the polypeptides, nucleic acid molecules and vectors encoding the polypeptides, and methods of use of the polypeptides or compositions, specifically for treating succinate-associate diseases and conditions are also provided.