Folates are essential for key biosynthetic processes in mammalian cells and play a crucial role in the maintenance of central nervous system homeostasis. Mammals lack the metabolic capacity for folate biosynthesis; hence, folate requirements are largely met through dietary sources. To date, three major folate transport pathways have been characterized: the folate receptors (FRs), reduced folate carrier (RFC), and proton-coupled folate transporter (PCFT). This article reviews current knowledge on the role of folate transport systems in mediating folate delivery to vital tissues, particularly the brain, and how these pathways are modulated by various regulatory mechanisms. We will also briefly highlight the clinical significance of cerebral folate transport in relation to neurodevelopmental disorders associated with folate deficiency.
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