CDC123 is an ATP-dependent protein-folding chaperone that facilitates assembly of the eukaryotic translation initiation factor 2 (eIF2) complex by binding to the gamma subunit and enabling subsequent association with alpha and beta subunits 12. The protein's mechanism involves ATP-dependent conformational changes in eIF2γ that expose binding sites for other eIF2 subunits, with ATP binding being functionally critical while eIF2α binding ultimately displaces CDC123 to complete assembly 12. Beyond translation initiation, CDC123 plays cell cycle regulatory roles through eIF2γ abundance control 3. Disease relevance spans multiple conditions: mutations affecting CDC123-mediated eIF2 assembly are associated with MEHMO syndrome, an X-linked intellectual disability 2. In cancer, CDC123 is highly expressed in breast and hepatocellular carcinomas, with expression positively correlating with poor prognosis; CDC123 knockdown impairs proliferation by disrupting cell cycle progression 45. In metabolic disease, CDC123/CAMK1D genetic variants associate with altered pancreatic beta-cell function and type 2 diabetes risk, affecting insulin secretion responses 67. Clinically, CDC123 represents a potential therapeutic target for cancer intervention through the USP9X/CDC123 regulatory axis 4.