Ouabain, a substance obtained from plant extracts, has been long known as cardiotonic, as well as by its high affinity to the Na-K- ATPase pump. The recent finding that ouabain is endogenously expressed in mammals has prompted research to determine its role as a hormone. We have shown that, in a physiological level (10 nM), it influences on three important features of epithelial physiology related to cell to cell contacts: (1) It modifies the Tight Junction integrity, as reflected by an increase in the Transepithelial Electrical Resistance (TER) of mature monolayers of MDCK cells. (2) It speeds up ciliogenesis, a feature closely related to epithelial (Apical/Basolateral) polarity and (3) It triggers Gap Junctional Intercellular Communication (GJIC). Since lack of GJIC has been associated to cancer, ouabain may be an interesting player on this issue.