TRPC genes encode a family of ion channel proteins that appear to be responsible for Ca2+ influx following stimulation of membrane receptors linked to phospholipase C. TRPC channels are thought to be tetrameric, and there is growing evidence to suggest heteromultimeric channel assembly. However, the channel subunit composition in vivo and the rules governing subunit assembly remain largely unknown. Like the Drosophila TRP channels, the mammalian TRPCs may reside in large signalling complexes localized to subcellular microdomains by interaction with specific PDZ-containing scaffolding proteins. Selective localization within cellular signalling networks may play an important role in the mode of channel activation following receptor stimulation. Evidence for heteromultimeric TRPC channel assembly gleaned from overexpression studies will be reviewed and recent evidence for the selective association of native TRPC channel subunits in rat brain will be discussed.