The 5’ untranslated region (5’UTR) of the ornithine decarboxylase (ODC) mRNA contains an internal ribosomal entry site (IRES). Mutational analysis of the ODC IRES has led to the identification of sequences necessary for cap-independent translation of the ODC mRNA. To discover novel IRES-trans-acting-factors (ITAFs), we performed a proteomic screen for proteins that regulate ODC translation using the wild-type ODC mRNA and a mutant version with an inactive IRES. We identified two RNA-binding proteins that associate with the wild-type ODC IRES, but not the mutant IRES. One of these RNA-binding proteins, PCBP2, is an established activator of viral and cellular IRESs. The second protein, ZNF9 (myotonic dystrophy type-2 protein), has not previously been shown to bind IRES-like elements. Using a series of biochemical assays, we validated the interaction of these proteins with ODC mRNA. Interestingly, ZNF9 and PCBP2 biochemically associate with each other and appear to function as part of a larger holo-ITAF / RNP complex. Our functional studies show that PCBP2 and ZNF9 stimulate translation of the ODC IRES. Importantly, these results may provide insight into the normal role of ZNF9 and why ZNF9 mutations cause myotonic dystrophy.