Forms a receptor-activated non-selective calcium permeant cation channel. Acts as a cell-cell contact-dependent endothelial calcium entry channel. Probably operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Mediates cation entry, with an enhanced permeability to barium over calcium. May also be activated by intracellular calcium store depletion. Interacts with TRPC4AP (By similarity). Homotetramer and heterotetramer with TRPC1 and/or TRPC5 (PubMed:12032305). Isoform alpha but not isoform beta interacts with ITPR1, ITPR2 and ITPR3 (PubMed:11163362). Interacts with (via PDZ-binding domain) with SLC9A3R1/NHERF (PubMed:12154080). Interacts with MX1 and RNF24 (PubMed:15757897, PubMed:17850865). Interacts (via CIRB domain) with SESTD1 (via spectrin 1 repeat) (PubMed:20164195). Interacts with CDH5 and CTNNB1 (PubMed:19996314). Interacts with SPTAN1 (via C-terminal spectrin repeats) and SPTBN5 (via C-terminus) (PubMed:18048348). Interacts (via protein 4.1-binding domain) with EPB41L2 (PubMed:16254212). Interacts with PLSCR1 (By similarity). Enhanced insertion into the cell membrane after activation of the EGF receptor. Strongly expressed in placenta. Expressed at lower levels in heart, pancreas, kidney and brain. Expressed in endothelial cells. Isoform alpha was found to be the predominant isoform. Isoform beta was not found in pancreas and brain. The protein 4.1-binding domain (654-685) is required for binding to EPB41L2 and channel activation. The calmodulin- and inositol 1,4,5-trisphosphate receptor-binding (CIRB) domain (695-724) is sufficient for the interaction with SESTD1. The spectrin-binding domain (730-758) is required for binding to SPTAN1 and SPTBN5. Phosphorylation modulates TRPC channel function by regulating the level of TRPC4 at the cell surface and by increasing the association with SLC9A3R1/NHERF. The interaction with spectrin is important in controlling the translocation of TRPC4 channels to the plasma membrane following EGF stimulation. The cell membrane presentation, the calcium entry function and the interaction with junctional proteins (CTNNB1 and CDH5) are controlled by endothelial cell-cell contacts. Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC4 sub-subfamily.