The TRPP Signaling Module: TRPP2/Polycystin-1 and TRPP2/PKD1L1

TRPP ion channels assemble with polycystin-1 family proteins into receptor-channel complexes. TRPP2–Polycystin-1 is required to coordinate renal three-dimensional tissue organization, whereas TRPP2–PKD1L1 is essential for establishment of left–right asymmetry during early embryonic development. The availability of orthologous and heterologous animal models made it feasible not only to characterize the function of single genes, but also to combine gene deficiencies and/or gene overexpression to establish molecular interdependencies. Canonical and noncanonical Wnt signaling have been associated with polycystic kidney disease. Furthermore, PRKCSH and SEC63 have been implicated in TRPP/polycystin protein maturation. Putative targets for therapeutic agents have set the stage for clinical intervention studies. The purpose of this review is to critically summarize recent in vivo evidence and to highlight inconsistencies that should be resolved if an accurate understanding of TRPP channels and polycystins is to be achieved. It is hoped that a deeper understanding of associated phenotypes will help to design rational therapies for autosomal dominant polycystic kidney disease.