Synucleins are small, highly conserved proteins in vertebrates, especially abundant in neurons and typically enriched in presynaptic terminals, α-Synuclein protein and a fragment of it, called NAC, have been found in association with pathological lesions of neurodegenerative diseases. Recently, mutations in a α-synuclein gene have been reported in families susceptible to an inherited form of Parkinson's diseases. In addition, α-synuclein has been implicated in the pathophysiology of other neurodegenerative diseases, including Alzheimer's disease and multiple system atrophy. Far less is known about other members of the synuclein family, β- and γ-synucleins. γ-synuclein is up-regulated in several types of cancer and may affect the integrity of the neurofilament network, while its bovine ortholog, synoretin, activates the Elk-1 signal transduction pathway. In this paper, we present data about the localization and properties of human and bovine γ-synuclein in several neuronal and non-neuronal cell cultures derived from ocular tissues. We show that γ-synuclein is present in the perinuclear area and is localized to centrosomes in several types of human interphase cells and in bovine retinal pigment epithelium. In mitotic cells, γ-synuclein staining is localized to the poles of the spindle. Further, overexpression of synoretin in retinoblastoma cells up-regulates MAPK and Elk-l. These results support the view that γ-synuclein is a centrosome protein that may be involved in signal transduction pathways. © 2001 Wiley-Liss, Inc.