Gem belongs to the Rad/Gem/Kir (RGK) subfamily of Ras-related GTPases, which lack typical C-terminal amino acid motifs for isoprenylation. Rad and Gem bind calmodulin in a Ca2+-dependent manner via this C-terminal extension, involving residues 278–297 in human Rad. High intracellular Gem levels, which interact with intact microtubules and microfilaments, promote profound changes in cell morphology. Ectopic Gem expression is sufficient to stimulate cell flattening and neurite extension in N1E-115 and SH-SY5Y neuroblastoma cells, suggesting a role for Gem in cytoskeletal rearrangement and/or morphological differentiation of neurons. Gem was also observed in developing trigeminal nerve ganglia in 12.5 day mouse embryos, demonstrating that Gem expression is a property of normal ganglionic development. The interaction of Gem with beta-subunits regulates Ca2+ channel expression at the cell surface. The human Gem gene maps to chromosome 8q22.1.