These results suggest that pde-1 and pde-5 redundantly function in AFD, possibly by hydrolyzing cGMP that temporally or spatially should not exist, to suppress Ca2+ increment in response to warming below threshold, to sharply decrease Ca2+ in response to cooling, and therefore to limit the temperature range to which AFD responds, which is essential for proper thermotaxis. Here, PDE5A is linked to Nager acrofacial dysostosis.