Elusive chloride channels. Chloride channels, in particular CA-activatad ones (CaCCs), are major regulators of sensory transduction, epithelial secretion, and smooth muscle contraction. They play also crucial roles in algae action potential and in generation and prevention of polyspermia in egg membrane. The research is described how some molecular candidates with properties characteristic of most CaCCs in native cells were identified using axolotl oocytes as an expresive system. The TMEM16A were identified as the oocyte CaCC. The TMEM16 family of transmembrane proteins with yet unknown function is conserved among eukaryotes, with family members linked to tracheomalacia (mouse TMEM16A), gnathodiaphysical dysplasia (human TMEM16E), aberrant X segregation (a Drosophila TMEM16 family member) and increased sodium tolerance (yeast TMEM16). The identification of this new family of ion channels may help the development of Ca CC antibodies and modulators for treating serious diseases such as hypertension or cystic fibrosis.