Although loss of ANKMY2 does not fully reverse final cyst progression in embryonic-onset ADPKD and only partially ameliorates disease in adult-onset disease, our results strongly suggest that adenylyl cyclases are key ciliary factors—though not the sole contributors—that are derepressed upon polycystin loss in both embryonic- and adult-onset disease. This evidence concerns the gene ANKMY2 and autosomal dominant polycystic kidney disease.