TRPP2 (polycystin-2) is a member of the TRP family of non-selective cation channels that is mutated in human autosomal polycystic kidney disease. It is thought to function together with polycystin-1 (PKD1), a large plasma membrane integral protein, as part of a multiprotein complex involved in transducing Ca2+-dependent mechanosensitive information in renal epithelial cells. TRPP2 has been implicated in Ca2+-dependent pathways in a variety of biological functions and species, including cell proliferation, sperm fertilization, mating behavior and asymmetric gene expression. Although its function as a Ca2+-permeable cation channel is well established, its precise role, regulation and subcellular localization in plasma membrane, endoplasmic reticulum and cilium have remained controversial. The present review summarizes the most pertinent recent evidence regarding the structural and functional properties of TRPP2 channels, focusing on the regulation and physiology of mammalian TRPP2.