In pancreatic ductal adenocarcinoma, RhoA is spatially regulated to the rear and leading edges of cells, leading to cancer cell invasion (Timpson et al. 2011); in brain and breast tumor cells, a RhoA-specific guanine nucleotide exchange factor, Syx, moves to the membrane, where it activates RhoA and downstream effector Dia1 and suppresses ROCK activity, resulting in polarized cancer cell migration (Dachsel et al. 2013); and NG2, a membrane proteoglycan, promotes amoeboid invasiveness of carcinoma cells through the activation of Rho (Pankova et al. 2012). Here, PLEKHG5 is linked to cancer.