ITPRIPL1/CD3L1 His Tag Protein, Cynomolgus

ITPRIPL1 (inositol 1,4,5-trisphosphate receptor‑interacting protein-like 1), also known as CD3L1 (CD3ε ligand 1), is a type I single-pass transmembrane protein. It lacks the immunoglobulin-like domain commonly found in conventional immune checkpoints; its extracellular domain (ECD) contains three functional regions, among which the RBD1 region exhibits the ability to inhibit T-cell cytotoxicity, while RBD2 and RBD3 show relatively weaker functions. Functionally, ITPRIPL1 directly binds to CD3ε on the T‑cell surface via its ECD, leading to sustained binding of Nck to the intracellular domain of CD3ε, which competitively inhibits the recruitment and phosphorylation of ZAP70, thereby blocking the TCR-CD3 signaling pathway and reducing calcium influx. This exerts immunosuppressive effects at the critical "signal one" stage of T-cell activation. ITPRIPL1 is highly expressed in normal testicular tissues to maintain immune privilege, and it is also broadly overexpressed in multiple human tumors, particularly in tumors with low or no PD-L1 expression. Based on this mechanism, neutralizing antibodies targeting ITPRIPL1 have demonstrated T-cell activation and tumor growth inhibition in various mouse tumor models, and have also achieved significant therapeutic effects in spontaneous tumors in companion animals.