Schematic representation of the polycystins. A. Polycystin-1 is a large plasma membrane receptor that undergoes a series of cleavage events to generate several different species co-existing within the same cell and most likely carrying out distinct functions. The protein exists as an uncleaved polypeptide of 4302 amino acids (aa) (I) and can be cleaved at its G-protein coupled proteolytic site, generating an N-terminal fragment (NTF) that can be released (II) or remain tethered to the C-terminal fragment (CTF) (III) . Two additional products generated by cleavage at yet-to-be-identified sites release either the entire C-terminal tail (IV)  or the last 112 aa (V) . B and C. PC-1 and PC-2 have been shown to interact through coiled-coil domains located in their cytoplasmic C-terminal tail. The precise localization and topology of the complex remains to be determined. The two proteins might co-localize at the plasma membrane, where PC-2 would regulate calcium influx from the extracellular compartment (A) . This might occur in some subcellular compartments such as the primary cilium. Alternatively, the plasma membrane pool of PC-1 might interact with the endoplasmic reticulum (ER) pool of PC-2, regulating its calcium release from the ER (B) .