The present disclosure is directed to compositions and methods related to an alpha sKlotho variant or fragment, in which 1 to up to about 20 amino acids have been deleted from the C-terminus, optionally also having mutations at V563 and/or K795. The present disclosure also pertains to an alpha sKlotho polypeptide variant or fragment, having mutations at V563 and/or K795, wherein the polypeptide variant or fragment is full-length, or optionally 1 to up to about 20 amino acids have been deleted from the C-terminus. The present disclosure also pertains to fusion polypeptides comprising: (a) an alpha sKlotho, in which 1 to up to about 20 amino acids have been deleted from the C-terminus, optionally also having mutations at V563 and/or K795； (b) a linker； and (c) FGF23, optionally having a mutation at R179, C206 and/or C244, or (c) serum albumin.本發明係關於與其中已自C末端缺失1個至至多約20個胺基酸、視情況亦在V563及/或K795處具有突變之α可溶克洛索(sKlotho)變體或片段相關之組合物及方法。本發明亦係關於在V563及/或K795處具有突變之α可溶克洛索多肽變體或片段，其中該多肽變體或片段為全長或視情況已自該C末端缺失1個至至多約20個胺基酸。本發明亦係關於融合多肽，其包含：(a)α可溶克洛索，其中已自該C末端缺失1個至至多約20個胺基酸，其視情況亦在V563及/或K795處具有突變；(b)連接體；及(c)FGF23，其視情況在R179、C206及/或C244處具有突變，或(c)血清白蛋白。
