The fibroblast growth factor receptor substrate (FRS)-2 protein family comprises FRS2alpha, a well-known central mediator for fibroblast growth factor signaling, and FRS2beta, whose endogenous expression pattern and function are not yet defined. Immunohistochemical analysis revealed that expression of FRS2beta was restricted to neural tissues and it colocalized with Tuj1, a neuronal marker. There are two distinct patterns of FRS2beta expression in neural cells: punctate and cup/ring-shaped; moreover, some particles colocalized with lysosomes. Stimulation with brain-derived neurotrophic factor (BDNF) enhanced FRS2beta phosphorylation and the cup/ring-shaped pattern. These results suggest a probable role of FRS2beta in the intracellular degradation systems of neural cells, which involves lysosomes.