Sugen kinases (SgK)269 (also known as PEAK1), and SgK223, an orthologue of rat pragmin and mouse NACK, are human pseudokinases that are implicated in the progression of several cancers. Both are scaffolding proteins that recruit distinct repertoires of signalling proteins and regulate a variety of biological endpoints including cell migration and invasion. To date, SgK269 and SgK223 have been largely studied as separate signalling entities. However, recent work has demonstrated that SgK269 and SgK223 undergo homo- and heterotypic association that determines signal output and biological response. Further characterization of the mechanism of action of these two pseudokinases will provide novel insights into how they promote cancer progression and may reveal novel therapeutic strategies. Here we review their structure, mechanism and function and roles they play in cancer pathogenesis.