Epithelia not only separate an organism from the external environment but also provide a diffusion barrier between internal fluid compartments. Occluding junctions between epithelial cells – namely tight junctions in vertebrates and septate junctions (SJs) in invertebrates – are key to establishing epithelial barrier function. In Drosophila, two types of SJs exist: pleated SJs (pSJs) are located in ectodermal epithelia, whereas smooth SJs (sSJs) are primarily found in epithelia of endodermal origin, such as the midgut. A number of pSJ proteins have been identified, but the components of sSJs have remained largely unknown. Here, Mikio Furuse and co-workers (p. 1980) identify Snakeskin (Ssk) as a protein that specifically associates with sSJs. Ssk localises to sSJs in the Drosophila midgut and Malpighian tubules and is required for sSJ formation. A lack of Ssk in Drosophila larvae results in defects in sSJ formation, alters epithelial cell morphology and impairs the barrier function of the midgut epithelium. The authors conclude that further experiments are required to fully elucidate the role of Ssk in sSJ formation and epithelial cell morphogenesis. Nevertheless, these observations provide an important starting point to further elucidate the components and function of sSJs in invertebrates.