PLEKHA5 and PLEKHA6 are newly identified proteins from the PLEKHA family which harbor a N-terminal tandem of WW domains that bind to PDZD11, similarly to the junctional protein PLEKHA7. PLEKHA5 and PLEKHA6 have a tissue distribution and subcellular localization distinct from PLEKHA7, since they are present at lateral cell-cell contacts, and additionally along microtubules in the case of PLEKHA5 and at junctions concerning PLEKHA6. Key structural domains, i. e. WW, PH and coiled-coil motifs, direct the distinct subcellular distributions of WW-PLEKHAs (PLEKHA5, PLEKHA6 and PLEKHA7), defining different subcellular pools of PDZD11. By promoting the binding of PDZD11 with the C-terminal PDZ-binding domain of the Menkes copper pump ATP7A, WW-PLEKHAs together with PDZD11 mediate the copper-induced distribution of ATP7A from the trans-Goli network to the cell periphery in polarized kidney epithelial cells, and are required to limit the increase of intracellular copper levels when cells are exposed to elevated copper conditions.