DPH6 encodes an amidase that catalyzes the final step of diphthamide biosynthesis, a critical post-translational modification of translation elongation factor 2 (EEF2) 1. The protein functions as a diphthamide synthetase, catalyzing an ATP-dependent amidation reaction that converts methylated diphthine to diphthamide 1. This modification is conserved across archaeal and eukaryotic organisms and represents one of the most complex post-translational modifications on proteins, requiring seven Dph proteins (Dph1-7) for complete biosynthesis 1. Diphthamide itself serves as the target for diphtheria toxin and other ADP-ribosylating toxins, making DPH6-mediated modification physiologically essential. Beyond its role in protein modification, DPH6 has been associated with glaucomatous optic nerve damage, with suggestive genetic associations identified in Latino populations for vertical cup-disc ratio, a clinical measure of glaucomatous damage 2. Additionally, DPH6 variants show suggestive associations with intraoperative anesthetic requirements in genome-wide association studies, though these did not reach genome-wide significance thresholds 3. The gene's role in disease pathogenesis remains incompletely understood and warrants further investigation.