U2O5 is the boundary composition between the fluorite and the layered structures of the UO2→3 system and the least studied oxide in the group. δ-U2O5 is the only layered structure proposed so far experimentally, although evidence of fluorite-based phases has also been reported. Our DFT work explores possible structures of U2O5 stoichiometry by starting from existing M2O5 structures (where M is an actinide or transition metal) and replacing the M ions with uranium ions. For all structures, we predicted structural and electronic properties including bulk moduli and band gaps. The majority of structures were found to be less stable than δ-U2O5. U2O5 in the R-Nb2O5 structure was found to be a competitive structure in terms of stability, whereas U2O5 in the Np2O5 structure was found to be the most stable overall. Indeed, by including the vibrational contribution to the free energy using the frequencies obtained from the optimized unit cells we predict that Np2O5 structured U2O5 is the most thermodynamically stable under ambient conditions. δ-U2O5 only becomes more stable at high temperatures and/or pressures. This suggests that a low-temperature synthesis route should be tested and so potentially opens a new avenue of research for pentavalent uranium oxides.