Using RNA interference (RNAi) to suppress gene expression, we attempted to identify tyrosine kinases involved in the extension of neurites from SH-SY5Y cells. A comprehensive analysis of gene "knock-down" profiles with small interfering RNAs (siRNAs) revealed candidate proteins that might control neurite extension. Phenotype-based screening of differentiating SH-SY5Y cells following retinoic acid (RA) stimulation indicated that twinfilin-2 is a protein that is involved in neurite outgrowth, as confirmed by morphological analysis of twinfilin-2-overexpressing cells.