The initiation of protein synthesis in eukaryotic cells is regulated by interactions between protein initiation factors and RNA molecules. Eukaryotic initiation factors (eIFs) are utilized in a sequence of reactions that lead to 80S ribosomal assembly and, ultimately, translation. The eukaryotic initiation factor-3 (eIF3) scaffolding structure is the largest of the eIF complexes and includes eIF3 alpha, eIF3 beta, eIF3 gamma, eIF3 delta, all of which function to control the assembly of the 40S ribosomal subunit. Association of eIF3 proteins with the 40S ribosomal subunit stabilizes eIF2-GTP-Met-tRNAiMet complex association and mRNA binding, and promotes dissociation of 80S ribosomes into 40S and 60S subunits, thereby promoting the assembly of the pre-initiation complex. Overexpression of eIF3 proteins is common in several cancers, suggesting a role for eIF3 proteins in tumorigenesis.