Dolichol kinase (DOLK)

Dolichol kinase is an essential membrane-bound enzyme (EC 2.7.1.108) encoded by the DOLK gene in humans, responsible for catalyzing the CTP-mediated phosphorylation of dolichol to form dolichyl phosphate, the terminal and rate-limiting step in de novo biosynthesis of dolichyl monophosphate[3][1][2]. Dolichyl phosphate acts as a lipid carrier necessary for N-linked glycosylation, O- and C-mannosylation, and the synthesis of glycosylphosphatidylinositol (GPI) anchors in the endoplasmic reticulum. These glycosylation pathways are vital for protein folding, stability, trafficking, and cellular signaling across all eukaryotes[1][2][3]. Deficiencies or mutations in dolichol kinase result in a rare, autosomal recessive congenital disorder of glycosylation (DOLK-CDG, CDG-Im), characterized by multi-system clinical manifestations including cardiomyopathy, severe neurological impairment, and dermatologic symptoms[2][3]. The DOLK protein is a hydrophobic transmembrane enzyme with distinct N-terminal (regulatory/structural) and C-terminal (catalytic) domains, and is evolutionarily conserved across eukaryotes, archaea, and some bacteria[1]. No drugs are currently approved to target DOLK directly. Diagnostic approaches focus on genetic confirmation and characterization of glycosylation status[2]. The most significant clinical challenge involves multisystem consequences of glycosylation failure caused by DOLK loss-of-function, with cardiac involvement being life-threatening in severe cases[2][3].

Other names

DK1KIAA1094TMEM15CDG1MSEC59Dolichol kinase 1Transmembrane protein 15SEC59 homologDolichol phosphokinaseCTP:dolichol O-phosphotransferase

Not applicable—no specific small-molecule or biologic therapies, but enzyme deficiency leads to hypoglycosylation due to impaired dolichol phosphorylation