EIF2S3 encodes the gamma subunit of eukaryotic translation initiation factor 2 (eIF2), which plays a crucial role in protein synthesis initiation 1. The eIF2 complex forms a ternary complex with GTP and initiator methionyl-tRNA, recruiting it to the 40S ribosomal subunit for start codon selection 2. Assembly of the heterotrimeric eIF2 factor is facilitated by Cdc123, which binds to the gamma subunit 3. EIF2S3 is also essential for regulation of the integrated stress response (ISR) 1. Pathogenic variants in EIF2S3 cause MEHMO syndrome, a severe X-linked disorder characterized by intellectual disability, epilepsy, hypogonadism, microcephaly, and obesity 1. Frameshift mutations typically cause severe phenotypes, while missense variants result in milder symptoms 4. The gene shows tissue-specific expression in developing pituitary gland and pancreatic islets, with mutations leading to hypopituitarism and glucose dysregulation including neonatal hypoglycemia followed by early-onset diabetes 25. EIF2S3 mutations also cause congenital hyperinsulinism in some cases 6. Loss of function results in impaired protein synthesis, increased cell death, and relaxed start codon selection stringency 24.