Among the six actin isoforms described in mammals, two are found in virtually all cells (?- and ?-cytoplasmic), two are detected in smooth muscle cells (?- and ?-smooth muscle) and two are present in striated muscles, one predominantly in skeletal (?-skeletal) and one in cardiac (?-cardiac) muscle cells. These actin isoforms differ slightly in their N-terminus, but the sequence of each of these actins is highly conserved in higher vertebRates. ?- and ?-cytoplasmic actin play crucial roles during various key cellular processes. Whereas ?-actin is preferentially localized in stress fibers, circular bundles and at cell-cell contacts, suggesting a role in cell attachment and contraction, ?-actin displays a more versatile organization, according to cell activities. In moving cells, ?-actin is mainly organized as a meshwork in cortical and lamellipodial structures, suggesting a role in cell motility. ?- and ?-actin depleted fibroblasts exhibit distinct changes in motility compared with their controls, suggesting a specific role for each isoform in cell locomotion.