FLVCR1-related diseases: from clinical heterogeneity to mechanistic insights

Feline Leukemia Virus subgroup-C Receptor 1 (FLVCR1) is an ubiquitously expressed choline and ethanolamine importer that is involved in the control of multiple aspects of cell biology including the regulation of phospholipids metabolism, heme homeostasis, mitochondria-ER contact sites and cellular bioenergetics. Mutations in the FLVCR1 gene cause a spectrum of autosomal-recessive disorders mainly affecting the nervous system. Research conducted in the last decade highlighted the complexity of the clinical features associated with FLVCR1 mutations, ranging from dysfunction of specific sensory modalities to severe neurodevelopmental defects. Despite important progress in understanding the FLVCR1 function, the molecular mechanisms responsible for the disease are still poorly understood and specific treatment for the affected patients is lacking. This review aims to critically examine the current knowledge surrounding FLVCR1-related diseases, from clinical manifestations to the underlying molecular mechanisms. We also propose future directions to advance research and improve patient treatment.