The classical process to recover uranium (U) and plutonium (Pu) from used nuclear fuel using tributyl phosphate (TBP), namely the Plutonium Uranium Redox EXtraction (PUREX) process, is complicated by the persistent presence of neptunium (Np) and thus requires extra purification steps. The concept of Adapted PUREX seeks to achieve Np recovery by adjusting the valence of the metal more effectively, thereby controlling its behavior more precisely. This study introduces the use of an aqueous hydroxypyridinone chelator, 3,4,3-LI(1,2-HOPO) (abbreviated as HOPO), to dictate the behavior of Np for recovery and meanwhile simplify cumbersome reprocessing steps. The interactions between Np and HOPO were probed mechanistically by way of absorption spectrophotometry, in conjunction with cyclic voltammetry. UV–Vis-NIR spectra illustrated the reduction of NpO22+ to Np4+, with a fast reaction rate. Cyclic voltammetry revealed quasi-reversible processes between the oxidized and reduced forms of the ligand and its Np complexes. The corresponding heterogeneous rate constants (k0) were estimated from the peak-to-peak separation potentials (ΔEp), at ~ 4 – 35 μm/s for both HOPO and NpHOPO, with scan rates of 0.01 – 0.4 V/s. Meanwhile, the electromotive force (EMF) as well as the change of Gibbs free energy (ΔG) were assessed from the half-wave potential (E1/2), demonstrating the completeness of NpO22+ reduction to Np4+ by HOPO. The cumulative formation constant of the resulting NpHOPO complex (logβ101) was determined by metal competition titration to be 42.0 ± 0.6, corroborating the extraordinarily high affinity of HOPO to tetravalent metal ions. The prowess of valence control by HOPO and the high stability of the formed complex resulted in enhanced separations of Np from U and of Pu from U, with a maximum separation factor of ~7000 for both, nearly 90- and 10300-fold higher, respectively, than the values obtained using conventional PUREX formulae.