4-Hydroxy-3-methylbut-2-enyl diphosphate reductase (EC 1.17.1.2, isopentenyl-diphosphate:NADP+ oxidoreductase, LytB, (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate reductase, HMBPP reductase, IspH, LytB/IspH) is an enzyme in the non-mevalonate pathway. It acts upon (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (or "HMB-PP").(1) isopentenyl diphosphate + NAD(P)+ + H2O (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + NAD(P)H + H+ (2) dimethylallyl diphosphate + NAD(P)+ + H2O (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate + NAD(P)H + H+