Protein trafficking is an essential cellular process and required, for example, for cell signaling and membrane polarization. Problems in protein trafficking have been linked to many human diseases such as cancer and Alzheimer’s disease. We investigate the mechanisms of vesicle trafficking of apical proteins in Drosophila photoreceptor cells (PRCs). Individual ommatidia in the Drosophila compound eye house 8 PRCs that surround a matrix filled lumen. Our goal is to investigate the role of Rab proteins in vesicle trafficking of apical proteins including the photopigment Rhodopsin (Rh), which localizes to the rhabdomere, the apical determinant Crumbs (Crb), which is enriched in the stalk membrane, and the proteoglycan Eyes shut (Eys), which is secreted into the interrhabdomeral space. Rab proteins are universal regulators of vesicle transport and more than 30 Rab proteins are found in Drosophila. Rab11, for example, is important in the delivery of rhabdomere bound proteins like Rh (Satoh et al., 2005, Development. 132: 1487-1497). We have examined the localization of Eys, Crb, and Rh, in animals with compromised Rab proteins using available RNAi and dominant negative (DN) lines. One example is expression of RabX5-DN, which leads to the cytoplasmic accumulation of Rh. We are currently in the process of determining the subcellular localization and producing CRISPR mutants for select Rabs that show interesting trafficking defects.