Mfsd2a: A Physiologically Important Lysolipid Transporter in the Brain and Eye

Lipids and essential fatty acids are required for normal brain development and continued photoreceptor membrane biogenesis for the maintenance of vision. The blood-brain barrier and blood-eye barriers prohibit the free diffusion of solutes into the brain and eye so that transporter-mediated uptake predominates at these barriers. The major facilitator superfamily of transporters constitutes one of the largest families of facilitative transporters across all domains of life. A unique family member, major facilitator superfamily domain containing 2a (Mfsd2a) is a lysophosphatidylcholine (LPC) transporter expressed at the blood-brain and blood-retinal barriers and demonstrated to be the major pathway for brain and eye accretion of docosahexaenoic acid (DHA) as an LPC. In addition to LPC-DHA, Mfsd2a can transport other LPCs containing mono- and polyunsaturated fatty acids. Mfsd2a deficiency in mouse and humans results in severe microcephaly, underscoring the importance of LPC transport in brain development. Beyond its role in brain development, LPC-DHA uptake in the brain and eye negatively regulates de novo lipogenesis. This review focuses on the current understanding of the physiological roles of Mfsd2a in the brain and eye and the proposed transport mechanism of Mfsd2a.