Geranylgeranyl diphosphate (GGPP) synthase (GGPS) catalyzes the synthesis of GGPP, a molecule responsible for the C20-prenylation of protein and for the regulation of a nuclear hormone receptor. The deduced 300aa human protein contains 5 conserved domains consistent with prenyltransferases. Recombinant GGPS shows enzymatic properties associated with the synthesis of GGPP from farnesyl diphosphate and isopentenyl diphosphate. Mouse GGPS is regulated in several tissues in obesity and is induced during adipocyte differentiation. GGPS is increased 5- to 20-fold in skeletal muscle, liver, and fat of ob/ob mice. Western blot analysis detects a 2-fold overexpression of protein in muscle and fat but not in liver. Differentiation of mouse fibroblasts into adipocytes induces GGPS expression more than 20-fold.