Our bioinformatics analysis suggested that Ser104 also had a high probabiility as a PKA or PKG target (unpublished observations), leading us to investigate the impact of Ser102A, Ser104A or Ser102Ala/Ser104Ala double mutation on PDE5A functions, including susceptibility to substances related to migraine pathophysiology, subcellular localization, PDE activity and protein conformation. The gene discussed is PDE5A; the disease is migraine disorder.