Lasp1 is an actin-binding, signaling pathway-regulated phosphoprotein that is over-expressed in several cancers. siRNA knockdown in cell lines retards cell migration, suggesting the possibility that Lasp1 upregulation influences cancer metastasis. Herein, we utilized a recently developed gene knockout model to assess the role of Lasp1 in modulating non-transformed cell functions. Wound healing and tumor initiation progressed more rapidly in Lasp1^-/- mice as compared to Lasp1^+/+ controls. Embryonic fibroblasts (MEFs) derived from Lasp1^-/- mice also migrated more rapidly in vitro. These MEFs characteristically possessed increased focal adhesion numbers and displayed more rapid attachment as compared to wild-type MEFs. Differential microarray analyses revealed alterations in message expression for proteins implicated in cell migration, adhesion and cytoskeletal organization. Notably, the focal adhesion protein, lipoma preferred partner (LPP), a zyxin family member and putative Lasp1 binding protein, was increased ~2 fold. Because LPP gene disruption reduces cell migration, we hypothesize that LPP plays a role in enhancing the migratory capacity of Lasp1^-/- MEFs, perhaps by modifying the subcellular localization of other motility-associated proteins. The striking contrast in the functional effects of loss of Lasp1 in innate cells as compared to cell lines reveals distinct differences in mechanisms of motility and attachment in these models.