DPP8 is a cytosolic dipeptidyl peptidase that cleaves N-terminal dipeptides from proteins with proline or alanine at position 2 1. The protein shows ubiquitous tissue expression and functions as a 100-kDa monomeric enzyme with neutral pH optimum 1. Beyond its proteolytic activity, DPP8 serves as a critical regulator of innate immunity by inhibiting inflammasome activation. DPP8 prevents caspase-1-dependent pyroptosis in resting monocytes and macrophages by sequestering cleaved C-terminal fragments of NLRP1 and CARD8 inflammasomes, blocking their oligomerization and activation 2. This regulatory function is essential for maintaining cellular homeostasis, as DPP8/9 inhibitors can induce pyroptosis in human myeloid cells through CARD8 activation 2. DPP8 has significant clinical relevance in cancer therapy, where selective inhibition shows promise as a therapeutic strategy for acute myeloid leukemia and other hematological malignancies 23. Additionally, DPP8 contributes to kidney disease pathogenesis, promoting ferroptosis in tubular epithelial cells during acute kidney injury and facilitating extracellular matrix deposition in mesangial cells 45. The development of selective DPP8 inhibitors represents an active area of drug development for both cancer and inflammatory diseases.