Hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes (PubMed:15673286). Has cAMP phosphodiesterase activity in vitro but not in vivo (PubMed:15673286). Has a role regulating cGMP transport in Malpighian tubule principal cells (PubMed:16232123). 3',5'-cyclic GMP + H2O = GMP + H(+) Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions. Inhibited by sildenafil and zaprinast. Interacts with PrBP. Expressed on the apical side of the Malpighian tubule principal cell polarized membrane. Loss of prenylation causes protein location to the cytoplasm. Expressed in Malpighian tubule principal cells (PubMed:16232123, PubMed:15673286). Also expressed in adult head (PubMed:15673286). Flies display increased active transport of cGMP. Overexpression of Pde6 confers inhibition of the active transport and efflux of cGMP by tubules. Belongs to the cyclic nucleotide phosphodiesterase family. Truncated N-terminus.