EEF1D encodes eukaryotic translation elongation factor 1 delta, a multifunctional protein with roles in both translation and transcriptional regulation. As a core component of the eEF1B complex, EEF1D acts as a guanine exchange factor (GEF) to facilitate eEF1A recycling during translational elongation 1. Beyond this canonical role, EEF1D exists as multiple alternatively spliced isoforms with distinct functions 2. The long isoform regulates heat-shock-responsive genes through association with heat shock transcription factors and direct DNA binding at heat shock promoter elements 2. Biallelic pathogenic variants in EEF1D cause severe autosomal recessive neurodevelopmental disorder characterized by intellectual disability, microcephaly, spasticity, and failure to thrive, with variants affecting either the alternatively spliced domain or the GEF domain 134. EEF1D has also emerged as a oncogenic factor in multiple cancers, where protein stabilization through binding partners like LGALS9B or SRSF9 activates PI3K/AKT signaling to promote proliferation and metastasis in gastric cancer, colorectal cancer, and glioma 567. These findings establish EEF1D as a critical regulator of both protein synthesis machinery and stress response pathways, with dysregulation contributing to neurodevelopmental and malignant disease.