Ca2+ signalling influences many processes during early development, including organogenesis, but the pathways through which intracellular Ca2+ acts remain elusive. On p. 3387, Rob Tombes and colleagues show that, during pronephric kidney development in zebrafish, the conserved calmodulin-dependent protein kinase CaMK-II is an effector of the Ca2+ channel PKD2 (a polycystin that is mutated in the ciliopathy autosomal dominant polycystic kidney disease, ADPKD). The researchers show that activated CaMK-II is present during early zebrafish development in the pronephric kidney and in other ciliated tissues. Pronephric duct formation fails in both PKD2-deficient and CaMK-II-deficient embryos, they report, and both types of embryo develop kidney cysts and have destabilised cloacal cilia. Importantly, PKD2 suppression inactivates CaMK-II in pronephric cells and cilia, whereas constitutively active CaMK-II restores pronephric duct formation in PKD2-deficient embryos. The researchers conclude that CaMK-II is a crucial PKD2 target that promotes pronephric kidney development and stabilises primary cloacal cilia, and suggest that CaMK-II could provide a therapeutic target for ADPKD and other ciliopathies.