Duchenne muscular dystrophy (DMD) is a fatal genetic disorder caused by mutations in the dystrophin gene and affecting up to one in 3500 males. Understanding the role of dystrophin (Dys) in the etiology of DMD will benefit from a comprehensive approach combining the individual advantages of multiple model systems. Therefore we are developing a pipeline to compare Dys interactor function in C. elegans and Drosophila. Lack of dystrophin in C. elegans leads to impaired burrowing, muscle decline, and death. In the DMD suppressor strain JPS518 (Beron et al. 2015; Genes, Brain & Behavior 14:357), one such interacting mutation displays large "blooms" of ectopic f-actin accumulation at the termini of the body wall muscles in response to muscle challenge. This suggest a novel mechanism for the restoration of muscle function in dystrophic worms. In Drosophila, Dys has been shown to be essential for two developmental events, the correct specification of the wing crossveins and the elongation of the egg during late oogenesis. Both phenotypes extend to new Dys insertion alleles from the Drosophila Gene Disruption Project. A GFP protein trap in the endogenous Dys locus shows that Dys has relatively low abundance and is very specifically localized at the basal side of epithelia such as the egg chamber follicle cells (as in Schneider et al. 2006; Dev. 133:3805). Dys-GFP accumulates laterally only in certain large cells, e.g., the egg chamber nurse cells and the salivary gland. Dys-GFP signal shows diverse, non-uniform patterns on the membrane; in the oocyte follicle cells it is circumferentially banded like actin. The Dys phenotypes and distributions allow for sensitive genetic and/or localization assays of candidate interactors such as the adaptor protein Capon/NOS1AP (C. elegans DYC-1). The Drosophila ortholog of Capon (CG42673) was identified and found to have conserved PTB and coiled coil domains, indicating participation in a protein complex, but it lacks the C-terminal Nitric Oxide Synthase binding region known in vertebrates. Capon LOF allelic combinations are viable and lack the short-egg phenotype seen in Dys mutants, but they do have defects in wing venation. The results indicate that a comparative approach will provide greater insights into the signaling and structural roles of the Dys complex and its functional partners.