DPP9 Antibody (YA7755)

Dipeptidyl peptidase 9 (DPP9) is a cytosolic post-proline serine protease that functions as a key endogenous regulator of innate immune homeostasis through control of inflammasome signaling pathways^[1]. Mechanistically, DPP9 directly interacts with the function-to-find domain (FIIND) of NLRP1 and contributes to maintenance of NLRP1 in an inactive state through both its peptidase activity and scaffolding function^[1]. This regulatory mechanism suppresses downstream inflammasome activation, thereby limiting caspase-1 activation, interleukin-1β maturation, and pyroptotic cell death^[1][2]. In disease-associated contexts, disruption of the DPP9-NLRP1 interaction, including germline mutations that impair FIIND-dependent binding, results in inflammasome hyperactivation and is linked to autoinflammatory disorders^[1]. Structural studies further demonstrated that DPP9 sequesters the bioactive C-terminal fragment of NLRP1 and functions as a checkpoint that restrains spontaneous inflammasome activation^[2]. Compared with the closely related isoform DPP8, DPP9 has been extensively characterized as a direct binding partner and negative regulator of both NLRP1 and CARD8 inflammasome sensors, highlighting a distinct role in inflammasome control beyond shared enzymatic activity^[1][3]. For experimental applications, pharmacological DPP8/9 inhibitors, including Val-boroPro (VbP), disrupt DPP9-mediated repression and activate NLRP1- or CARD8-dependent inflammasome signaling, making these compounds valuable tools for studying inflammasome biology, pyroptosis, and inflammatory disease mechanisms^[1][2][3].