Choline kinase beta (CHKB)

Choline kinase beta is an enzyme encoded by the CHKB gene that catalyzes the first phosphorylation step in the biosynthesis of phosphatidylcholine and phosphatidylethanolamine, two major phospholipids crucial for eukaryotic cell membrane integrity and mitochondrial function[1][4][8]. The enzyme participates in the Kennedy pathway, primarily in tissues such as skeletal muscle, brain, and bone, and its loss causes “megaconial” congenital muscular dystrophy characterized by abnormal mitochondria, muscle wasting, intellectual disability, and, in some cases, bone abnormalities[4][8]. Unlike choline kinase alpha (CHKA), which is linked to many cancers, CHKB functions mainly in normal development and homeostasis of muscle and neural systems, with little evidence for a direct oncogenic or cancer drug target role[4][8]. CHKB is essential for maintaining proper membrane lipid composition, mitochondrial respiration, and cellular energy balance, with mutations resulting in severe systemic phenotypes. While research inhibitors such as hemicholinium-3 can block CHKB activity, there are no approved drugs targeting this enzyme for therapeutic intervention, and inhibition carries a high risk of muscle and neurological toxicity[8].

Other names

Choline/ethanolamine kinase betaCKβEthanolamine kinase (EK)Choline kinase-like proteinCholine/ethanolamine kinase (CEK)CHK betaCHKEB

Competitive inhibition of choline kinase beta ATP/choline-binding site (by HC-3 and similar choline analogs); Altered function by phosphorylation via protein kinase A regulates enzymatic activity and inhibitor sensitivity