Loss of endoplasmic reticular (ER) Ca²⁺ activates store-operated Ca²⁺ entry (SOCE) by causing the ER localized Ca²⁺ sensor STIM to unfurl domains that activate Orai channels in the plasma membrane at membrane contact sites (MCS). Here we demonstrate a novel mechanism by which the inositol 1,4,5 trisphosphate receptor (IP₃R), an ER-localized IP₃-gated Ca²⁺ channel, regulates neuronal SOCE. In human neurons, SOCE evoked by pharmacological depletion of ER-Ca²⁺ is attenuated by loss of IP₃Rs, and restored by expression of IP₃Rs even when they cannot release Ca²⁺, but only if the IP₃Rs can bind IP₃. Imaging studies demonstrate that IP₃Rs enhance association of STIM1 with Orai1 in neuronal cells with empty stores; this requires an IP₃-binding site, but not a pore. Convergent regulation by IP₃Rs, may tune neuronal SOCE to respond selectively to receptors that generate IP₃.