RPIA (ribose-5-phosphate isomerase A) catalyzes the reversible conversion of ribose-5-phosphate to ribulose 5-phosphate, functioning as a key enzyme in the non-oxidative branch of the pentose phosphate pathway 1. This metabolic role is critical for nucleotide synthesis and cellular energy production, as RPIA contributes to precursor supply for DNA and RNA biosynthesis 2. RPIA expression is dysregulated in multiple cancer types. In colorectal cancer, RPIA is a direct target of tumor-suppressive miR-124, and RPIA knockdown reduces glucose consumption, ATP levels, and DNA synthesis, thereby inhibiting cancer cell proliferation 2. Similarly, in hepatocellular carcinoma, RPIA overexpression correlates with advanced clinical stage, increased tumor size, and enhanced invasion, with RPIA promoting proliferation through ERK signaling and PP2A inhibition 3. In endometrial cancer, SRC-2-mediated RPIA expression maintains glycolytic capacity and pentose phosphate pathway function required for cell proliferation 4. Beyond cancer, RPIA participates in physiological processes including trophoblast invasion and spiral artery remodeling during placentation through chemerin-mediated pentose phosphate pathway activation 5. RPIA also functions in lung aging and age-related disease development 6. In bacterial pathogenesis, RPIA cooperates in UDP-GlcNAc synthesis for exopolysaccharide production in Enterococcus faecalis 7. Hypoxic regulation of RPIA expression in glioma cells is modulated by IRE1 signaling 8.