Dolichol kinase (DK) catalyzes the CTP-mediated phosphorylation of dolichol, the final step in dolichyl monophosphate (Dol-P) biosynthesis. By phosphorylation of dolichol, DK enables the transfer of monosaccharides to Dol-P and the initiation of dolichol-linked oligosaccharide biosynthesis. Dol-P-Ma, generated from Dol-P, is utilized as a substrate for N-glycosylation, O-mannosylation and biosynthesis of GPI-anchored proteins [, , ]. In human, defects in dolichol kinase (DOLK, also known as transmembrane protein 15) are the cause of congenital disorder of glycosylation type 1M (CDG1M); also known as dolichol kinase deficiency. CDGs are a family of severe inherited diseases caused by a defect in glycoprotein biosynthesis. They are characterised by under-glycosylated serum glycoproteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation and maintenance of cell functions. CDG1M is a very severe disorder with death occurring in early infancy [].
