(please see [1]) Due to its role in the pentose phosphate pathway and the Calvin cycle, RpiA is highly conserved in most organisms, such as bacteria, plants, and animals.

All orthologs of the enzyme maintain an asymmetric tetramer quaternary structure with a cleft containing the active site.

[5] The separate molecules of the enzyme are held together by highly polar contacts on the external surfaces of the monomers.

[9] The protein encoded by RPIA gene is an enzyme, which catalyzes the reversible conversion between ribose-5-phosphate and ribulose-5-phosphate in the pentose-phosphate pathway.

In the oxidative part of the pentose phosphate pathway, RpiA converts Ru5P to the final product, R5P through the isomerization reaction (figure 3).

The oxidative branch of the pathway is a major source for NADPH which is needed for biosynthetic reactions and protection against reactive oxygen species.

RPIA is essential in the cycle, as Ru5P generated from R5P is subsequently converted to ribulose-1,5-bisphosphate (RuBP), the acceptor of carbon dioxide in the first dark reaction of photosynthesis (Figure 3).

[18] A significant increase in RpiA expression was detected both in tumor biopsies of HCC patients and in a liver cancer tissue array.

In addition, the ability of RpiA to regulate cell proliferation and colony formation in different liver cancer cell lines required ERK signaling as well as the negative modulation of PP2A activity and that the effects of RpiA could be modulated by the addition of either a PP2A inhibitor or activator.

[19] RpiA generated attention when the enzyme was found to play an essential role in the pathogenesis of the parasite Plasmodium falciparum, the causative agent of malaria.

Plasmodium cells have a critical need for a large supply of the reducing power of NADPH via PPP in order to support their rapid growth.

The R5P produced via increased pentose phosphate pathway activity is used to generate 5-phospho-D-ribose α-1-pyrophosphate (PRPP) needed for nucleic acid synthesis.

[17] Hence, designing drugs that target RpiA in Plasmodium falciparum could have therapeutic potential for patients that suffer from malaria.