Stimulation of cell surface receptors that increase phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis leads to intracellular Ca2+ release and activation of plasma membrane Ca2+ entry channels. Ca2+ entry via these channels regulates a wide array of physiological functions. The molecular composition of these channels and the mechanisms that activate or inactivate them have not yet been elucidated. Members of the TRPC subfamily of the TRP (transient receptor potential) family of proteins have been recently suggested as molecular components of these channels. In addition, Ca2+ signaling proteins and the signals they generate are compartmentalized and spatiotemporally regulated. Thus, the mechanisms involved in the assembly and trafficking of Ca2+ signaling proteins, including TRPC channels, will determine the regulation of Ca2+ entry and its effect on cellular function.