Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B. Can also form a functional, homotetrameric ion channel (PubMed:27214281). Functions as a cation channel involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (PubMed:12514735, PubMed:18695040, PubMed:27760766, PubMed:31048699). Functions as outward-rectifying K(+) channel, but is also permeable to Ca(2+), and to a much lesser degree also to Na(+) (PubMed:27760766). May contribute to the release of Ca(2+) stores from the endoplasmic reticulum (By similarity). Together with TRPV4, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). PKD1 and PKD2 may function through a common signaling pathway that is necessary to maintain the normal, differentiated state of renal tubule cells (PubMed:9568711, PubMed:10615132). Acts as a regulator of cilium length, together with PKD1. The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling. The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases flow-induced signaling (PubMed:20096584). Also involved in left-right axis specification via its role in sensing nodal flow; forms a complex with PKD1L1 in cilia to facilitate flow detection in left-right patterning (PubMed:21307093, PubMed:22983710). Detection of asymmetric nodal flow gives rise to a Ca(2+) signal that is required for normal, asymmetric expression of genes involved in the specification of body left-right laterality (PubMed:12062060, PubMed:21307093, PubMed:22983710). Channel activity is regulated by phosphorylation (By similarity). The channel is activated by increased cytoplasmic Ca(2+) (in the uM range) and by membrane depolarization (PubMed:27760766). Homotetramer. Heterotetramer with PKD1, giving rise to a complex formed by one PKD1 chain and three PKD2 chains (By similarity). Interaction with PKD1 is required for ciliary localization (PubMed:25405894). Isoform 1 interacts with PKD1 while isoform 3 does not (PubMed:16192288). Interacts with PKD1L1 (PubMed:21307093, PubMed:22983710). PKD1 requires the presence of PKD2 for stable expression (PubMed:16192288). Interacts with CD2AP (PubMed:10913159). Interacts with HAX1 (PubMed:10760273). Interacts with NEK8 (PubMed:18235101). Part of a complex containing AKAP5, ADCY5, ADCY6 and PDE4C (PubMed:21670265). Interacts (via C-terminus) with TRPV4 (via C-terminus) (PubMed:18695040). Interacts (via C-terminal acidic region) with PACS1 and PACS2; these interactions retain the protein in the endoplasmic reticulum and prevent trafficking to the cell membrane (PubMed:15692563). Interacts with TMEM33 (PubMed:31048699). PKD2 localization to the plasma and ciliary membranes requires PKD1. PKD1:PKD2 interaction is required to reach the Golgi apparatus form endoplasmic reticulum and then traffic to the cilia (PubMed:25405894). Detected on kidney tubule basolateral membranes and basal cytoplasmic vesicles (PubMed:9568711, PubMed:10770959). Retained in the endoplasmic reticulum by interaction with PACS1 and PACS2. Cilium localization requires GANAB (By similarity). Detected in kidney epithelium (at protein level) (PubMed:9568711, PubMed:10770959, PubMed:11854751). Highly expressed on basolateral membranes in distal convoluted tubules and medullary thick ascending limbs of Henle (PubMed:9568711). Detected at much lower levels in cortical and medullary collecting tubules, and not detected in the glomerular tuft, in thin limbs of Henle, interstitium and blood vessels (at protein level) (PubMed:9568711). Expressed in mesenchymally derived structures in the developing embryo at day 12.5. Isoform 1 is predominantly expressed in kidney at all developmental stages with high levels also detected in lung. Isoform 3 shows highest expression in brain with lower expression in kidney and lung, low levels in thymus and is hardly detectable in liver. Ubiquitous in embryos at the early somite stage. The C-terminal coiled-coil domain is involved in oligomerization and the interaction with PKD1. The isolated coiled-coil domain forms a homotrimer in vitro; the homotrimer interacts with a single PKD1 chain. The coiled-coil domain binds calcium and undergoes a calcium-induced conformation change (in vitro). N-glycosylated (PubMed:11854751). The four subunits in a tetramer probably differ in the extent of glycosylation; simultaneous glycosylation of all experimentally validated sites would probably create steric hindrance (By similarity). Phosphorylated (PubMed:16551655). Phosphorylation is important for protein function; a mutant that lacks the N-terminal phosphorylation sites cannot complement a zebrafish pkd2-deficient mutant. PKD-mediated phosphorylation at the C-terminus regulates its function in the release of Ca(2+) stores from the endoplasmic reticulum. PKA-mediated phosphorylation at a C-terminal site strongly increases the open probability of the channel, but does not increase single channel conductance. Complete embryonic lethality, with most embryos surviving up to about 16.5 dpc (PubMed:9568711, PubMed:10615132, PubMed:12062060). Embryos lacking Pkd2 develop normally up to 13.5 dpc, but after that about half of them display total body edema and focal hemorrhages (PubMed:10615132). Mutant embryos display defects in left-right laterality, including abnormal heart looping (PubMed:12062060). After 13.5 dpc, all embryos display defects in heart development, with defective formation of the interventricular septum (PubMed:10615132, PubMed:12062060). Besides, many display defective formation of the atrial septum and pericardial effusions (PubMed:10615132). After 14.5 dpc, the embryos display progressive cystic dilatation of pancreatic ducts (PubMed:10615132). After 15.5 dpc, they display progressive kidney cyst formation (PubMed:10615132). In contrast, liver development is normal, without any cyst formation (PubMed:10615132). Heterozygous mice with one null allele and one instable allele that leads to somatic loss of Pkd2 expression due to intragenic recombination all display bilateral renal cysts at an age of about 11 weeks (PubMed:9568711). These cysts cover 25-75% of the cut surface area of each kidney (PubMed:9568711). Progressive cyst formation leads eventually to renal failure and shortened lifespan (PubMed:10615132). Besides, these mice all display liver cysts and half of them display also bile duct proliferation (PubMed:9568711). About half of the heterozygous mice with one null allele and one instable allele that leads to somatic loss of Pkd2 expression due to intragenic recombination display visible pancreas cysts at an age of three months (PubMed:10615132). Mice homozygous for an instable allele that leads to somatic loss of Pkd2 expression due to intragenic recombination develop renal cysts that arise from cells that have lost Pkd2 expression (PubMed:9568711). Heterozygous mice that bear one null allele also have a reduced lifespan, but this is not due to kidney failure (PubMed:10615132). Minor isoform. Belongs to the polycystin family.