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Abstract: The de novo synthesis of the amino acid l-serine plays an essential role in the development and functioning of the central nervous system (CNS). l-Serine displays many metabolic functions during different developmental stages; among its functions providing precursors for amino acids, protein synthesis, nucleotide synthesis, neurotransmitter synthesis and l-serine derived lipids. Patients with congenital defects in the l-serine synthesizing enzymes present with severe neurological abnormalities and underscore the importance of this synthetic pathway. In this review, we will discuss the cellular functions of the l-serine pathway, structure and enzymatic properties of the enzymes involved and genetic defects associated with this pathway. [Copyright &y& Elsevier]