Major facilitator superfamily domain-containing protein 2A (MFSD2A) (MFSD2A)

Major facilitator superfamily domain-containing protein 2A (MFSD2A) is a sodium-dependent symporter that serves as the primary gateway for essential omega-3 fatty acids, specifically docosahexaenoic acid (DHA) in the form of lysophosphatidylcholine (LPC), into the brain and eyes [1, 3, 8]. Predominantly expressed in the endothelial cells of the blood-brain barrier (BBB), MFSD2A is critical for maintaining the barrier's low permeability by suppressing caveolae-mediated transcytosis through lipid remodeling of the cell membrane [4, 6]. Loss-of-function mutations in the MFSD2A gene lead to severe neurodevelopmental conditions, such as progressive microcephaly and intellectual disability, due to insufficient lipid uptake and subsequent BBB dysfunction [1, 3, 12]. In therapeutic contexts, MFSD2A is a dual-purpose target: its temporary inhibition is being investigated as a molecular switch to open the BBB for enhanced delivery of CNS-targeted drugs, such as nanoparticles or antibodies [4, 5, 10]. Conversely, its upregulation or activation is explored as a neuroprotective strategy to restore barrier integrity in conditions like ischemic stroke, Alzheimer's disease, and traumatic brain injury [5, 10, 13]. Additionally, MFSD2A acts as a tumor suppressor in lung and gastric cancers and is a potential biomarker for monitoring neurodegenerative progression and fetal development [9, 10, 11].

Other names

MFSD2NLS1MCPH15SLC59A1Sodium-dependent lysophosphatidylcholine symporter 1Sodium-dependent LPC symporter 1Major facilitator superfamily domain containing 2A

MFSD2A functions as a sodium-dependent symporter that transports lysophosphatidylcholine (LPC) lipids, particularly those containing docosahexaenoic acid (DHA), across the blood-brain barrier (BBB) [1, 3]. This transport process incorporates specific lipids into the endothelial cell membrane, which suppresses caveolae-mediated transcytosis, thereby maintaining the restrictive permeability of the BBB [4, 6].