The present disclosure provides compositions and methods relating to or derived from antigen binding proteins that activate FGF21-mediated signaling. In embodiments, the antigen binding proteins specifically bind to (i) ²-Klotho； (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4； or (iii) a complex comprising ²-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, the antigen binding proteins are fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to (i) ²-Klotho； (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4； or (iii) a complex comprising ²-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. Other embodiments provide nucleic acids encoding such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from type 2 diabetes, obesity, NASH, metabolic syndrome and related disorders or conditions.
