Members of the RAS subfamily of GTPases function in signal transduction as GTP/GDP-regulated switches that cycle between inactive GDP- and active GTP-bound states. Guanine nucleotide exchange factors (GEFs), such as Repac, serve as RAS activators by promoting acquisition of GTP to maintain the active GTP-bound state and are the key link between cell surface receptors and RAS activation. Repac, also known as Rap guanine nucleotide exchange factor 5 (RAPGEF5), is a 580 amino acid protein that is expressed in brain and testis, with weaker expression in heart, placenta, lung, pancreas and small intestine. Existing as two alternatively spliced isoforms, the Repac gene is conserved in cow, mouse and rat. The gene that encodes Repac maps to human chromosome 7p15.3, with high expression of this region linking to positive response to erlotinib therapy for those with non-small-cell lung cancer.