Insulin receptor substrate p53 (IRSp53) is a key player in cytoskeletal dynamics, interacting with the actin modulators WAVE2 and Mena. Here, we identified a PDZ protein, MALS, as an IRSp53-interacting protein using a yeast two-hybrid screen. A pull-down assay showed that IRSp53 and MALS interact through the PDZ domain of MALS and the C-terminal PDZ-binding sequence of IRSp53. Their interaction in MDCK cells was also demonstrated by co-immunoprecipitation. Immunocytochemistry showed the colocalization of IRSp53 and MALS at cell-cell contacts. Cytochalasin D induced the redistribution of both proteins to the cytosol. Thus, MALS is a partner of IRSp53 anchoring the actin-based membrane cytoskeleton at cell-cell contacts.