DHDDS (dehydrodolichyl diphosphate synthase subunit) encodes the catalytic subunit of the dehydrodolichyl diphosphate synthase complex, which forms with NUS1 to catalyze dolichol biosynthesis 1. DHDDS functions as a cis-prenyltransferase that catalyzes chain elongation of farnesyl diphosphate through multiple condensations with isopentenyl pyrophosphate, producing dehydrodolichyl diphosphate, a precursor for dolichyl phosphate 1. This dolichol serves as a sugar carrier essential for N-linked protein glycosylation in the endoplasmic reticulum 1. DHDDS mutations cause two distinct phenotypes. Autosomal recessive variants cause retinitis pigmentosa 59 (RP59), characterized by inner retinal degeneration and photoreceptor-bipolar cell synaptic dysfunction 2. Heterozygous de novo variants cause a neurodevelopmental and neurodegenerative disorder presenting with developmental delay, epilepsy, and progressive movement disorders including myoclonus, ataxia, and dystonia 3. Disease mechanisms extend beyond glycosylation defects; DHDDS patient cells show Niemann-Pick C-like endolysosomal dysfunction with cholesterol and ganglioside GM1 accumulation, suggesting impaired lysosomal trafficking and lipid homeostasis 4. Miglustat, an approved NPC therapy, improves these cellular phenotypes, offering potential therapeutic options 4. Clinical presentation shows variable symptom onset from infancy to adulthood with no clear genotype-phenotype correlation 5.