Every day, human renal tubules process 140 l of glomerular filtrate into 1 l of urine. They accomplish this by the coordinated function of distinct cell types occupying specific positions along the tubules. This precisely defined structure requires tight regulation of morphogenesis. A group of disorders termed polycystic kidney disease (PKD) is characterized by altered tubular morphology. Mutating genes involved in PKD results in renal tubules that either fail to form properly or 'forget' how to maintain their 'correct' diameter. Study of PKD proteins will elucidate the process of renal tubular morphogenesis and guide the development of therapies. Here, we focus on insights provided by study of the most common form of PKD, autosomal dominant PKD.