Integrating signals from the extracellular matrix through the cell surface into the nucleus is an essential feature of metazoan life. To date, many signal transducers known as shuttle proteins have been identified to act as both a cytoskeletal and a signaling protein. Among them, the most prominent representatives are zyxin and lipoma preferred (translocation) partner (LPP). These proteins belong to the LIM domain protein family and are associated with cell migration, proliferation, and transcription. LPP was first identified in benign human lipomas and was subsequently found to be overexpressed in human malignancies such as lung carcinoma, soft tissue sarcoma, and leukemia. This review portrays LPP in the context of human neoplasia based on a study of the literature to define its important role as a novel protooncogene in carcinogenesis.