The Jun N-terminal kinase pathway plays an important role in inducing programmed cell death (apoptosis) and is activated in a variety of contexts. The deubiquitinating enzymes (DUBs) are proteases regulating the protein stability by ubiquitin-proteasome system. Here, for the first time, we report the phenotypes observed during eye development that are induced by deleting Drosophila USP5 gene, which encodes one of the USP subfamily of DUBs. usp5 mutants displayed defects in photoreceptor differentiation. Using genetic epistasis analysis and molecular markers, we show that most of these phenotypes are caused by the activation of apoptosis and JNK pathway. These data may provide a mechanistic model for understanding the mammalian usp5 gene.