Transient receptor potential protein 4 (TRPC4) has been identified as a candidate for the capacitative calcium entry (CCE) channels, but its functional role is still controversial. Using a RT-PCR technique, a novel isoform of TRPC4, designated rTRPC4 γ, was isolated. It was nearly identical to full-length rTRPC4 (rTRPC4α), except that it lacked 53 nucleotides that correspond to the predicted linker between the second and third transmembrane domain of rTRPC4α, and its mRNA was expressed in brain and heart. This splice variant encoded a potential protein of 400 residues that consists of an amino-terminal cytoplasmic domain and 2 transmembrane domains by a frameshift mutation. When rTRPC4 γ cDNA was transiently transfected to HEK-293 cells, thapsigargin (TG)-induced Ca²⁺ entry was suppressed significantly. By contrast, expression of rTRPC4α did not affect TG-induced Ca²⁺ entry. To investigate the subcellular localization, plasmids were constructed with green fluorescence protein (GFP) as an amino-terminal fusion to rTRPC4 variants. GFP-rTRPC4γ fusion protein, unlike GFP-rTRPC4 α, was localized to the cytoplasm as well as plasma membrane. These results suggest that rTRPC4γ may play a modulatory role in CCE channel activity in the brain and heart. (Circ J 2002; 66: 954 - 958)