XPNPEP1 (X-prolyl aminopeptidase 1) is a metalloaminopeptidase that catalyzes removal of penultimate prolyl residues from N-terminal peptides, such as Arg-Pro-Pro 1. It contributes to degradation of bradykinin 1 and is a dual target alongside PEPD for inhibition studies on inflammasome activation 2. The gene is localized to chromosome 10.3 3. Cellularly, XPNPEP1 is primarily expressed in neurons within the hippocampus 4. The enzyme plays a critical role in preventing replication-associated genome instability; XPNPEP1 depletion causes double-strand break (DSB) accumulation in human mitotically-proliferating cells, though it is not required for DSB repair itself 5. XPNPEP1 deficiency causes neurological complications with hippocampal neurodegeneration, impaired learning and memory, and altered glial populations including reduced astrocytes and increased microglia density 4. The gene is also associated with disease susceptibility; it was identified as a risk factor in lung adenocarcinoma prognosis 6 and as a potentially druggable target linked to psychiatric disorder pathogenesis through immune-related mechanisms 7. Additionally, XPNPEP1 was identified as a susceptibility gene in rheumatoid arthritis 8.