The Drosophila Transient Receptor Potential (TRP) channel is the founding member of a large and diverse family of channel proteins. These channels are evolutionarily conserved from yeast to mammals and are found in many organisms and tissues. The TRP family is classified into seven subfamilies, while the most closely related to the Drosophila TRP are members of the TRPC (Canonical) subfamily. This review focuses on a comparison between properties of Drosophila TRP, discovered in the native photoreceptor cells, and that of mammalian TRPC channels. These properties include: (i) organization of TRP channels in multimolecular signaling complexes via PDZ-containing scaffold proteins, (ii) mutations causing constitutive activity of TRP channels and cell degeneration, (iii) regulation of TRP channels by phosphorylation, and (iv) hypoxia/anoxia-activation of TRP channels. Hence, we suggest that knowledge gained from studies of Drosophila may guide studies in mammals that attempt elucidating diverse types of diseases caused by TRPC channel malfunction.