SLC46A1 encodes the proton-coupled folate transporter (PCFT), which serves as the primary mechanism for intestinal folate absorption across the apical brush-border membrane of the proximal small intestine 1. PCFT functions as an electrogenic proton symporter that displays optimal folate and antifolate transport activity at acidic pH conditions 2. The transporter is also expressed in the choroid plexus, where it is required for folate transport into cerebrospinal fluid 3. Beyond folate transport, recent evidence suggests SLC46A1 plays a role in cellular iron homeostasis, with loss of expression leading to decreased iron content in hepatocellular carcinoma tissues 4. Mutations in SLC46A1 cause hereditary folate malabsorption (HFM), a rare autosomal recessive disorder characterized by severe systemic and cerebral folate deficiency 31. The gene can be epigenetically silenced through promoter methylation, particularly in leukemia cells where CpG island methylation leads to poor PCFT expression 5. Additionally, elevated SLC46A1 expression in breast tumors correlates with chemoresistance and reduced patient survival, suggesting its potential as a therapeutic target 6.