The morphological changes that take place during the process of neuronal differentiation, such as neurite outgrowth, axon development and branching of neurite prolongations, also require a finely tuned regulation of lipid biosynthesis, especially the formation of new membrane phospholipids. In mammalian cells, the biosynthesis of acyl-containing lipids employs saturated and monounsaturated fatty acids as preferential substrates. The abundance of these fatty acids is determined, in great part, by the Lomitapide Mesylate activity of StearoylCoA desaturases, key lipogenic enzymes that catalyze the conversion of SFA into MUFA. These fatty acid species, particularly MUFA, appear to be essential components for fetal brain development. Data from experiments performed in rats indicate that exogenous MUFA and SCD-derived MUFA are Orbifloxacin critical neurotrophic factors implicated in the modulation of axogenesis in brain. However, the potential implication of human SCDs in the mechanisms of neurogenesis and neuronal differentiation has remained understudied. Human tissues express two SCD variants, SCD1 and SCD5. Our lab and others have reported that SCD1, a D9desaturase isoform present in most mammalian tissues, plays a key role in the regulation of lipogenesis, cell cycle and programmed cell death in human normal and cancer cells. SCD5, a SCD isoform that was thought to be exclusive of primates but is also found in bovines, dogs and birds, is uniquely expressed in fetal brain, as well as in adult brain and pancreas, a distribution pattern that suggest that this enzyme may be implicated in critical neural functions. In this regard, it was recently reported that the expression of SCD5 mRNA was elevated in the brain of patients with Alzheimer’s disease. Unlike SCD1, the regulation and functional roles of SCD5 in human cells and tissues, especially in brain cell biology, have not been described to date. In the present study we show that constitutive expression of human SCD5 in mouse Neuro2a cells, a well-characterized cell model of neuronal differentiation, promotes a greater n-7MUFA-to-SFA ratio in total cell lipids and modifies the pattern of de novo synthesis of lipids. Concomitantly, SCD5 activity stimulated cell proliferation whereas it significantly suppressed the process of retinoic acid-induced differentiation of Neuro2a cells into mature neurons, suggesting a role for the desaturase in regulating the balance between cell expansion and differentiation of neuronal cells. We also provide evidence that signal transduction pathways that modulate these processes, such as epidermal growth factor receptor Akt/ERK and Wnt, are targeted for regulation by SCD5. Our data offer new insight into the role of SCD5 as a key factor in the coordinated regulation of lipogenic and signaling events that determine the biological fate of the neuronal cell. A complex synchronization of cell division, exit of cell cycle and differentiation is required for the proper development of the nervous system. The mechanisms of neuronal proliferation and differentiation involve an intricate array of biochemical and morphological changes that require a finely tuned modulation of signaling pathways and lipogenic routes. The particular pattern of expression of SCD5, with the highest levels in embryo and adult brain, suggest that a potential role for SCD5 in the mechanisms of proliferation and differentiation of neural cells. Here we report that ectopic expression of SCD5 induces a drastic phenotypical modification in Neuro2a cells, a terminal marker of the neuronal differentiation process.