Progressive cystic kidney degeneration underlies diverse renal diseases, including the most common cause of kidney failure, autosomal dominant Polycystic Kidney Disease (PKD). Genetic analyses of patients and animal models have identified several key drivers of this disease. The precise molecular and cellular changes underlying cystogenesis remain, however, elusive. Drosophila mutants lacking the translational regulator Bicaudal C (BicC, the fly ortholog of vertebrate BICC1 implicated in renal cystogenesis) exhibited progressive cystic degeneration of the renal tubules (so called “Malpighian” tubules) and reduced renal function. BicC bound to myc mRNA in tubules. Elevation of Myc protein levels caused tubular degeneration in BicC mutants. Activation of the Target of Rapamycin (TOR) pathway, another common feature of PKD, was found in BicC mutant flies. In flies rapamycin administration reversed substantially the cystic phenotype and improved survival. New mechanistic insight on BicC function leads us to propose Drosophila as a genetically tractable model for dissecting the evolutionarily-conserved molecular mechanisms of renal cystogenesis and for chemical and genetic screens to identify modifiers of the phenotype towards novel therapeutic strategies.