Autosomal dominant polycystic kidney disease (ADPKD) is one of the commonest monogenic diseases of man affecting 1:1000 of the worldwide population. In the UK, it is predicted that there are over 50,000 individuals with or at risk of inheriting this condition. It is characterised by a highly variable but progressive increase in the number and size of renal cysts that ultimately leads to renal failure in later life. Approximately 6-8% of patients receiving renal replacement therapy, such as dialysis or transplantation, have a diagnosis of ADPKD. It is also associated with vascular complications including hypertension, ischaemic heart disease and cerebral aneurysms. ADPKD is caused by mutations in PKD1 (85%) and PKD2 (15%). PKD1 and PKD2 encode polycystin-1 and polycystin-2 respectively. Polycystin-1 is a novel >650 kDa membrane associated glycoprotein containing up to 11 transmembrane domains. Its unique arrangement of extracellular and intracellular protein domains and motifs suggests a role in mechanosensitive signal transduction pathways. Polycystin-2 is a highly conserved member of the transient receptor potential (TRP) channel family. They associate to form a large mechanosensitive calcium-regulated calcium ion channel complex although independent functions have been identified. In polarised renal epithelial cells, polycystin-1 localises to focal adhesion complexes, cell-cell adhesion complexes and to the renal primary cilium. Polycystin-2 is localised in the ER and the primary cilium. Loss of normal cilial function regulated by a polycystin complex is thought to be the main pathogenic mechanism in ADPKD. Several studies have demonstrated the need for polycystin-1 and polycystin-2 to form a complex for plasma membrane localisation but the precise mechanisms that control the polarised distribution of these proteins are poorly characterised. Polycystin-1 has been technically difficult to study in many model systems. Chimeric proteins using the intracellular C-terminus of polycystin-1 have shown that this region contains specific targeting information directing ER/golgi export and polarised distribution to the lateral membrane. All 11 transmembrane domains and the intracellular C-terminus are required for cilial localisation. Deletion and mutagenesis studies have identified a short motif in the C-terminus of polycystin-1 responsible for ER/golgi export. As the majority of PKD1 mutations are truncating and 5′ to the region encoding this motif, ADPKD is likely to result from a failure of normal polycystin polarised trafficking. Intracellular levels of polycystin-1 are frequently increased in ADPKD supporting this hypothesis. The mechanisms responsible for the polarised trafficking of polycystin-2 have been more clearly elucidated although some discrepancies remain. PIGEA-14 and PACS proteins have been shown to have a role in polycystin-2 localisation via interaction with C-terminal domains whilst an N-terminal motif has been shown to be responsible for polycystin-1 independent cilial localization. I will review the current literature and present some new data that characterises the abnormalities in polarised sorting of the polycystins in ADPKD.