CASP10 (caspase-10) is a cysteine-type endopeptidase that functions as a key mediator of extrinsic apoptosis, particularly in primary human T cells where it operates alongside caspase-8 in death receptor signaling 1. The protein contains a death effector domain and acts as a positive regulator of the execution phase of apoptosis through involvement in the CD95 death-inducing signaling complex and ripoptosome [GO annotations]. CASP10 participates in multiple signaling pathways including canonical NF-κB signal transduction and exhibits cysteine reactivity that can be targeted by small-molecule ligands 12. Pathogenic variants in CASP10 cause autoimmune lymphoproliferative syndrome (ALPS), a rare genetic disorder characterized by defective lymphocyte apoptosis, resulting in abnormal accumulation of double-negative T cells, lymphadenopathy, and splenomegaly 345. CASP10 polymorphisms, particularly rs13006529, rs13010627, and rs3900115, have been associated with cancer susceptibility 6. Additionally, CASP10 serves as a prognostic biomarker in small cell lung cancer and other malignancies, with expression levels correlating with diagnosis, prognosis, and sensitivity to anticancer drugs 72. Somatic CASP10 mutations occur infrequently (2.4%) in acute leukemias and multiple myelomas but may contribute to disease pathogenesis in affected patients 8.