Although modulators of Cdc42 have not been investigated directly in ALS, it is interesting to note that ALS2 encodes alsin2, which carries a DH/PH domain and elicits GEF properties potentially for all three classical members of Rho GTPases (i.e., RhoA, Rac1, and Cdc42; Hadano et al., 2001). Here, ALS2 is linked to amyotrophic lateral sclerosis.