Clinical spectrum and pathogenesis of nephronophthisis

Nephronophthisis (NPH) comprises a group of autosomal recessive cystic kidney diseases and is the most frequent genetic cause of end-stage renal disease in children and adolescents. Causative mutations in more than a dozen genes have been identified that encode for the NPH protein family. Almost all of these proteins localize to primary cilia leading to the classification of NPH as a ciliopathy. The purpose of this review is to highlight the latest research on the molecular pathogenesis of the ciliopathy NPH.Recent identification of novel disease causing genes and research on the localization and signaling function of nephrocystins have paved the way to a more detailed understanding of the molecular and cellular pathology of NPH and associated ciliopathies.Here we discuss the most recently identified NPH related genes, the role of the NPH protein complex in ciliary biology and recently discovered functions of NPH proteins in cellular signaling.