Molecular chaperones bind and stabilize proteins during folding and assembly, thereby insuring their proper function. UNC-45 is a molecular chaperone that plays an important role in folding of the protein myosin during stressful conditions. Myosins are key factors in cytokinesis, signal transduction and muscle contraction in many organisms. Improper folding and subsequent malfunction of myosin has been associated with cardiomyopathies and skeletal muscle disease. Besides binding myosin, UNC-45 also partners with HSP-90, Apobec2 and with the GATA transcription factor. This study seeks to uncover new interactions inDrosophila melanogaster UNC-45 through a genetic deficiency screening in an unc-45 sensitized background. We combined UNC-45 mutant heterozygotes with deficiency heterozygotes for individual segments of chromosomes 1, 2 and 3. The resulting offspring were identified and selected against dominant balancer markers. Organisms that carry a single copy of the unc-45 mutation as well as the deficiency in question served as our experimental group, whereas organisms that contain a single copy of the unc-45 mutation but lack the deficiency were used as controls. Thus far we have identified a deficiency region (7783) where the cross yielded lethality for double heterozygotes. This region of interest runs from bands 22E1 through 22F3 on chromosome 2, encompassing twenty-four genes. To narrow down candidate genes encoding possible UNC-45 interacting proteins, we selected RNAi lines directed against six of these genes. We then crossed these lines with an all-muscle driver and an indirect flight muscle (IFM) driver in the presence of normal and reduced levels of UNC-45 in order to replicate the lethal phenotype obtained with line 7783. The lethality has been putatively mapped to the SLY1- homologous (CG3539) gene. Body wall muscles of larvae with all-muscle SLY-1 homologous knock-down and reduced UNC-45 levels displayed minor defects in myofiber organization. Thus far, our studies point to SLY-1 homologous as an important gene involved in muscle function and development. Although a possible interaction was found between UNC-45 and SLY-1 homologous, further proof is needed for confirmation. Future studies include analysis of tissue-specific expression of SLY-1 homologous by qRT-PCR and in situ hybridization. Pull-down assays and mass spectrometry can also be used to verify interactions and to identify additional proteins interacting with UNC-45 during development and periods of stress. Findings from this study will further our understanding of the mechanism of action of UNC-45 and its possible role in skeletal and cardiac muscle diseases.