Identification and Physiological Analysis of Novel Riboflavin Transporter RFVT

Abstract

Riboflavin (vitamin B2) is an essential water-soluble vitamin that serves as a precursor for flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), key cofactors in biological redox reactions. These reactions are crucial for energy metabolism and cellular homeostasis. Mammals cannot synthesize riboflavin and rely on specialized transport systems for its absorption and distribution. The discovery of the riboflavin transporter (RFVT) family, comprising RFVT1 (SLC52A1), RFVT2 (SLC52A2), and RFVT3 (SLC52A3) has provided critical insights into riboflavin homeostasis. These transporters show tissue-specific expression and play essential roles in riboflavin uptake. Mutations in SLC52A2 and SLC52A3 have been linked to Brown–Vialetto–Van Laere syndrome (BVVLS), a rare neurodegenerative disorder characterized by progressive sensorineural hearing loss and cranial nerve dysfunction. Functional studies using knockout mouse models have demonstrated that Rfvt deficiency results in embryonic lethality or severe neurological impairment due to impaired riboflavin transport. Patients with BVVLS and RFVT mutations showed symptomatic improvement with high-dose riboflavin supplementation. This review summarizes the molecular characteristics, physiological functions, and pathological implications of RFVTs and emphasizes their role in disease mechanisms and potential therapeutic strategies. Understanding the riboflavin transport mechanisms provides a foundation for developing targeted treatments for riboflavin-related disorders.