NKTR (natural killer cell triggering receptor) is a peptidyl-prolyl cis-trans isomerase that catalyzes proline isomerization to facilitate protein folding and serves as a component of a putative tumor-recognition complex involved in NK cell function. The gene is expressed in multiple cellular compartments and binds cyclosporin A, consistent with its PPIase activity. In colorectal cancer, NKTR expression is significantly lower in primary tumors with liver metastasis compared to those without metastasis 1. Experimental knockdown of NKTR in colorectal cancer cells increases cell proliferation, migration, and invasion in vitro, suggesting that reduced NKTR expression may promote metastatic progression 1. Clinically, NKTR has been a focus for drug development targeting IL-2 signaling pathways. NKTR-214 (bempegaldesleukin), an IL-2 receptor βγ-biased agonist designed to preferentially activate CD8+ T and NK cells without expanding regulatory T cells, demonstrated clinical activity in advanced solid tumors with manageable tolerability 2, though it did not meet primary endpoints in phase 3 trials for metastatic melanoma and renal cell carcinoma 3. NKTR-255, a polymer-conjugated IL-15 receptor agonist, showed promise when combined with CAR T-cell therapy in relapsed/refractory B-cell acute lymphoblastic leukemia, achieving 89% measurable residual disease-negative remission with doubled progression-free survival at 12 months versus historical controls 4.