Solute carrier family 44 member 4 (SLC44A4) (SLC44A4)

Solute carrier family 44 member 4 (SLC44A4), also known as the human thiamine pyrophosphate transporter (hTPPT), is a multi-pass membrane protein essential for the cellular uptake of pyridoxine (vitamin B6) and thiamine pyrophosphate (UniProt Q53GD3). It is primarily expressed in the apical membrane of intestinal epithelial cells, particularly in the colon, where it facilitates the absorption of vitamins produced by the gut microbiota and those obtained from the diet (PMID: 23812005). Recent studies have identified SLC44A4 as the principal transporter for the pyridoxine form of vitamin B6 in the human gut, operating via a sodium-independent and amiloride-sensitive mechanism (PMID: 28213610). Other transporters, such as SLC25A32, facilitate the movement of the active form, pyridoxal 5-phosphate, into mitochondria (PMID: 29330376). Beyond its physiological role, SLC44A4 is clinically significant due to its association with ulcerative colitis; specific genetic polymorphisms in the SLC44A4 gene are linked to increased disease susceptibility, potentially due to localized vitamin deficiencies (PMID: 26192915). While not a traditional target for antagonistic therapy, it is a critical factor in nutritional pharmacology and the management of inflammatory bowel conditions. Its activity is vital for maintaining the levels of B6 and thiamine required for numerous enzymatic reactions in energy metabolism and neurotransmitter synthesis. Understanding the regulation of these transporters is key to addressing malabsorption syndromes and optimizing the delivery of B6-based therapeutics.

Other names

Human thiamine pyrophosphate transporterhTPPTCholine transporter-like protein 4CTL4Pyridoxine transporterSLC44A4

SLC44A4 mediates the sodium-independent, pH-dependent, and carrier-mediated uptake of pyridoxine and thiamine pyrophosphate across the plasma membrane, particularly in the large intestine (PMID: 28213610).