The Drosophila light activated channel TRP is the founding member of a large and diverse family of channel proteins that is conserved throughout evolution. These channels are Ca2+ permeable and have been implicated as important component of cellular Ca2+ homeostasis in neuronal and non-neuronal cells. The power of the molecular genetics of Drosophila has yielded several mutants in which constitutive activity of TRP leads to a rapid retinal degeneration in the dark. Metabolic stress activates rapidly and reversibly the TRP channels in the dark in a constitutive manner by a still unknown mechanism. The link of TRP gating to the metabolic state of the cell is shared also by mammalian homologues of TRP and makes cells expressing TRP extremely vulnerable to metabolic stress, a mechanism that may underlie retinal degeneration and neuronal cell death.