Anoctamin 1 (ANO1) or TMEM16A gene encodes a member of Ca2+ activated C1-channels(CaCCs) that are critical for physiological functions,such as epithelial secretion,smooth muscle contrac-tion and sensory signal transduction.The attraction and interest in ANO1/TMEM 16A arise from a decade long investigations that abnormal expression or dysfunction of ANO1 is involved in many pathological phenotypes and diseases,including asthma,neuropathic pain,hypertension and cancer.However,the lack of specific modulators of ANO1 has impeded the efforts to validate ANO1 as a therapeutic target.This review focuses on the recent progress made in understanding of the pathophysiological functions of CaCC ANO1 and the current modulators used as pharmacological tools,hopefully illustrating a broad spectrum of ANO1 channelopathy and a path forward for this target validation.