SERINC2 encodes the serine incorporator 2 which functions as a l-serine transmembrane transporter (Fig. 1 and Table 3). l-serine plays an essential role in neuronal development and function. l-serine serves as a precursor in the synthesis of l-cysteine, sphingolipids, and the neuromodulators d-serine and glycine, which modulate excitatory NMDA receptors and inhibitory glycine receptors in the brain (Snell, 1984). l-serine is a non-essential amino acid; however, its de novo synthesis within the brain is essential because of the limited permeability of the blood–brain barrier for l-serine (Smith, 2000). l-serine is generated in astrocytes and requires a dedicated amino-acid transporter for entry into neuronal cells by ASCT1 (alanine-serine-cysteine transporter) which is highly similar in structure and function to SERINC2 (Yamasaki et al., 2001). Mutations in the gene encoding ASCT1 results in a brain disorder characterized by developmental delay, microcephaly and hypomyelination (Damseh et al., 2015). In addition, knockout of Asct1 in mice results in a significant decrease in brain glycine levels, deficits in glycine neurotransmission and a hyperekplexia-like phenotype. The clinical and pre-clinical phenotypes resulting from genetic variation in the cellular
