TRPC1 of the transient receptor potential protein family is a cationic channel subunit that is commonly associated with calcium entry activated by store-depletion (Beech et al. 2003). Full length TRPC1 mRNA is derived from 13 putative exons encoding 793 amino acids. Several alternatively spliced isoforms have been observed (Zitt et al. 1996; Sakura & Ashcroft. 1997) and may account for functional diversity, but they remain to be characterised. RT-PCR was used to screen for expression of alternatively spliced TRPC1 transcripts in RNA samples from human brain, aorta, saphenous vein and HEK 293 cells. Calcium imaging was used to study splice variant physiological function. Ethical approval was obtained for use of human tissue. Data are given as mean ± s.e. mean and data sets compared by unpaired Student’s t-tests. Sequencing of PCR products confirmed the detection of nine novel alternatively spliced transcripts. Many of these variants contained exon deletions which would cause a frameshift and lead to reading of a premature termination codon (PTC). Five transcripts contained a deletion of exon 2 which would lead to early truncation and potentially inefficient translation. One mRNA expressed in all tissues contained a 284 bp deletion corresponding to loss of exons 8 and 9. Both exons are presumably skipped due to use of an alternative acceptor site at the start of exon 10 instead of exon 8. Frameshift would lead to a PTC early in exon 10. Hence the mRNA is predicted to encode a 464 amino acid isoform truncated within the putative second transmembrane domain, named TRPC1-∆8,9. Calcium imaging was used to investigate the functional effect of TRPC1-∆8,9 on calcium entry in HEK 293 cells store depleted using 1µM thapsigargin. Re-entry of calcium after store depletion was inhibited by 29.7% (∆F340/F380 was 0.045±0.0037 (n=12 experiments) compared to 0.064±0.005 (n=10) for the vector control P<0.005). Rate of calcium entry was also significantly lower in TRPC1- ∆8,9 expressing cells (P<0.002).This study identifies several novel alternatively spliced variants of TRPC1. One of the splices may be a repressor of store-operated calcium entry.