Triplet U@C-1(28324)-C-80, violating the isolated pentagon rule, is experimentally recognized as the stable isomer for uranium-based endohedral monometallofullerene U@C-80. Here we first verified that triplet U@D-3(31921)-C-80, following the isolated pentagon rule, was to be another thermodynamically stable isomer via density functional theory in conjunction with statistical thermodynamic analysis. U@D-3(31921)-C-80 was probably missing in the previous experiment and would be a promising isomer in the to-be experiment because of its excellently thermodynamic stability. In addition, the anomalous metal position was revealed in U@D-3(31921)-C-80 and U@C-1(28324)-C-80. Four-electron transfer from U to C-80 was also revealed for the two isomers. Thus, two unpaired Sf electrons were still in the U for U@D-3(31921)-C-80 and U@C-1(28324)-C-80. Moreover, the covalent interactions between U and C-80 in U@D-3(31921)-C(80 )were stronger than those in U@C-1(28324)-C-80. The electrostatic interactions preponderated in the interaction energy Delta E-int between U and C-80 for U@C-1(28324)-C-80, and the orbital interactions dominated in the Delta E(int )for U@D-3(31921)-C-80. The electrophilic and nucleophilic reactivities were also analyzed for U@D-3(31921)-C-80 and U@C-1(28324)-C-80. Electronic circular dichroism spectra were simulated to distinguish the two enantiomers of U@C-1(28324)-C-80. We are hopeful that this investigation will be valuable for further identification of the two enantiomers in future experiments.