INTRODUCTION: Aberrant Ca OBJECTIVES: We investigated the impact of NCX1- and TRPA1-mediated Ca METHODS: The cell experiments were conducted using the human normal colonic epithelial cell line (HCoEpiC) and human colon cancer cell lines (Caco-2, SW620, and DLD-1). We performed stable transfection to knock down NCX1 or TRPA1 genes and employed CCK8, colony formation, and flow cytometry assays to assess cell proliferation. We employed RT-qPCR, Western blotting, immunofluorescence and co-immunoprecipitation assays to explore the expression and regulatory relationship between NCX1 and TRPA1. Calcium and sodium assays were used to determine [Ca RESULTS: NCX1 and TRPA1 were parallelly over-expressed, co-localized, and bound, and their functional activities were enhanced in human CC cells. NCX1 functions in Ca CONCLUSION: TRPA1 channels couple with the Ca