Choline transporter-like 1, CTL1, also known as SLC44A1, CD92, and CHTL1, is a member of the broader SLC44A family and is an approximately 70 kDa choline/H⁺-antiporter across both plasma and mitochondrial membranes¹. 

The CTL1 protein consists of nine transmembrane (TM) domains, with an intracellular N-terminus and an extracellular C-terminus. Sequence alignment of SLC44A proteins from rats, mice, and humans reveals homology in four TM domains (TM2, TM6, TM8, and TM9), with TM8 and TM9 exhibiting the highest conservation, suggesting that these TM domains may contain critical functional regions, including potential substrate-choline binding sites. The presence of negatively charged aspartic acid (D) and glutamic acid (E) residues at the C-terminus of CTL1 strongly suggests their involvement in binding and transport of positively charged choline and protons.¹

CTL1-mediated choline transport is believed to be involved in phospholipid and betaine synthesis, and it may also play a role in choline transport for acetylcholine synthesis in non-neuronal cells. CTL1 exhibits an intermediate affinity for choline, with a K_min value in the low micromolar range. CTL1 is selectively inhibited by the choline analogue hemicholinium-3 (CH-3).^1,2

CTL1 has been identified as a biomarker of monocytic cell differentiation, and its expression is elevated in differentiated dendritic cells. Aberrant choline metabolism is a hallmark of malignant transformations, and the activation of the CTL1 gene has been associated with anomalous cell-cycle regulators.^1,2

Loss of function of the CTL1 protein is implicated in neurodegenerative disease states and can lead to symptoms including ataxia, dysarthria, tremor, swallowing difficulties, and cognitive decline, as well as leukoencephalopathy and cerebellar atrophy. On a cellular level, the main effect of CTL1 deficiency is a significant reduction in choline transport, which is compensated by using membrane phosphatidylcholine as an internal source of choline. As a response to this crucial need for choline and phosphatidylcholine, there is a depletion of inner membrane phospholipids, specifically phosphatidylethanolamine and phosphatidylserine, as well as a deficiency in very long-chain fatty acids (VLCFAs). Collectively, these features represent the primary abnormality and the major causes of impaired plasma membrane and organelle function in CTL1 deficiency. ³