HPD (4-hydroxyphenylpyruvate dioxygenase) is a metabolic enzyme catalyzing conversion of 4-hydroxyphenylpyruvic acid to homogentisic acid in tyrosine catabolism, with highest expression in liver tissue 1. The gene spans approximately 21 kb of genomic DNA organized into 14 exons and 13 introns, with transcriptional regulation involving cyclic adenosine monophosphate signaling 1. Beyond its canonical metabolic function, HPD possesses an unexpected moonlighting role as an RNA-binding protein (RBP) containing two dsRNA-binding domains (RBDs) 2. Through RRACH motif recognition, HPD promotes translation of glycolytic enzymes including triosephosphate isomerase (TPI) and alpha-enolase (ENO1), thereby sustaining ovarian cancer glycolysis, tumor growth, and chemotherapy resistance 2. Clinically, loss-of-function mutations in HPD cause rare inherited disorders: hawkinsinuria and tyrosinemia type 3. The discovery of HPD's RBP function represents a paradigm shift in understanding its role in cancer pathogenesis, as targeting the RBD domain disrupts both RNA binding and glycolytic flux, offering potential therapeutic strategies 2. This dual enzymatic-RNA binding functionality expands the functional repertoire of metabolic proteins in cancer biology beyond traditional metabolic roles.