With NUS1, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery. Both subunits contribute to enzymatic activity, i.e. condensation of multiple copies of isopentenyl pyrophosphate (IPP) to farnesyl pyrophosphate (FPP) to produce dehydrodolichyl diphosphate (Dedol-PP), a precursor of dolichol phosphate which is utilized as a sugar carrier in protein glycosylation in the endoplasmic reticulum (ER) (PubMed:25066056, PubMed:28842490, PubMed:32817466). Synthesizes long-chain polyprenols, mostly of C95 and C100 chain length (PubMed:32817466). Regulates the glycosylation and stability of nascent NPC2, thereby promoting trafficking of LDL-derived cholesterol (PubMed:21572394). (2E,6E)-farnesyl diphosphate + n isopentenyl diphosphate = di-trans,poly-cis-polyprenyl diphosphate + n diphosphate Binds 1 magnesium ion per subunit. Activated by phospholipids including cardiolipin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine. Values were measured with the heterodimer. kcat is 0.58 sec(-1) with (2E,6E)-farnesyl diphosphate and isopentenyl diphosphate as substrate. Optimum pH is 8-9. Active from pH 5.5 to 9.3. Protein modification; protein glycosylation. Lipid metabolism. Forms an active dehydrodolichyl diphosphate synthase complex with NUS1 (PubMed:25066056, PubMed:28842490, PubMed:32817466). Interacts with NPC2 (PubMed:21572394). colocalizes with calnexin. Expressed at high levels in testis and kidney. Expressed in epididymis (at protein level). Slightly expressed in heart, spleen and thymus. The catalytic site at NUS1-DHDDS interface accomodates both the allylic and the homoallylic IPP substrates to the S1 and S2 pockets respectively. The beta-phosphate groups of IPP substrates form hydrogen bonds with the RXG motif of NUS1 and four conserved residues of DHDDS (Arg-85, Arg-205, Arg-211 and Ser-213), while the allylic isopentenyl group is pointed toward the hydrophobic tunnel of the S1 pocket where the product elongation occurs. The disease is caused by variants affecting the gene represented in this entry. The disease may be caused by variants affecting the gene represented in this entry. May be due to exon skipping. Belongs to the UPP synthase family.