Lysine-specific demethylase 1 (LSD1) is a known regulator of epigenetic marks throughout the genome, but new data from Miller and colleagues have revealed a new, non-catalytic role for LSD1 in regulating AKT activation in colorectal cancer cells. The cover depicts a chromatin immunoprecipitation-massively parallel DNA sequencing (ChIP-seq) heatmap demonstrating the global abundance of histone 3 bearing dimethylated lysine 4 (H3K4me2) throughout the genome of colorectal cancer cells. LSD1 knockdown in colorectal cancer cells had little effect on global H3K4me2 distribution and AKT pathway modulation was not explained by a change in H3K4me2 signal, thus suggesting an alternative mechanism underlying the observation. For more information, see the Highlight on page 183 and the article on page 264.