DHRSX is an oxidoreductase enzyme located on the pseudoautosomal regions of the X and Y chrX|Y that plays a critical role in dolichol biosynthesis, an essential step in N-linked protein glycosylation 1. DHRSX catalyzes two non-consecutive reactions in the three-step conversion of polyprenol to dolichol: first, it performs NAD+-dependent dehydrogenation of polyprenol into polyprenal, and subsequently catalyzes NADPH-dependent reduction of dolichal into dolichol, with SRD5A3 catalyzing the intermediate step 1. This dual substrate and cofactor specificity is unique among dolichol biosynthetic enzymes 1. Deficiency of DHRSX causes congenital disorder of glycosylation type 1DD (DHRSX-CDG), presenting as pseudoautosomal-recessive disease with missense variants disrupting enzyme function 1. Loss of DHRSX function results in accumulation of polyprenol derivatives and depletion of dolichol, severely impairing N-glycosylation capacity 23. Beyond its established role in glycosylation, DHRSX may act as a positive regulator of starvation-induced autophagy, functioning as a non-classical secretory protein 4. DHRSX has also been identified as a candidate gene in nonobstructive azoospermia 5, suggesting additional reproductive functions.