EIF2D is a non-canonical translation initiation factor that delivers initiator and elongator tRNAs to the ribosomal P-site in a GTP-independent manner 1. Unlike canonical eIF2, eIF2D functions when eIF2α is phosphorylated under stress conditions, enabling continued translation of specific mRNAs 1. Structurally, eIF2D contains C-terminal domains resembling eIF1 (involved in codon selection) and a SWIB/MDM2 fold unique among translation initiation factors 1. Beyond initiation, eIF2D promotes 40S ribosomal subunit recycling during intrinsic ribosome destabilization through its winged helix domain, which distinguishes it functionally from the MCTS1-DENR complex 2. eIF2D also facilitates translation reinitiation at upstream open reading frames (uORFs), though this function differs mechanistically from MCTS1-DENR-dependent reinitiation 3. Dysregulation of eIF2D and other translation factors is associated with psychoneurological and neurodegenerative diseases, making eIF2D a potential diagnostic biomarker 4. Notably, eIF2D does not participate in hepatitis C virus IRES-driven translation under standard conditions 5. These findings establish eIF2D as a multifunctional factor critical for stress-responsive translation, ribosome recycling, and reinitiation.