ADA2 (adenosine deaminase 2) is a secreted enzyme that catalyzes the degradation of extracellular adenosine, a signaling molecule regulating cellular responses 1. The enzyme exhibits elevated activity at high adenosine concentrations and binds cell surfaces through proteoglycans, suggesting roles beyond its catalytic function 2. ADA2 is highly expressed in myeloid cells and plays a critical role in macrophage differentiation 2. Deficiency of ADA2 (DADA2), caused by loss-of-function mutations in CECR1, is an autosomal recessive monogenic vasculitis syndrome first described in 2014 31. Reduced ADA2 levels lead to increased extracellular adenosine, triggering a proinflammatory cascade and endothelial dysfunction 1. Endothelial instability stems from abnormal proinflammatory macrophage development 4. DADA2 presents with early-onset vasculitis, ischemic/hemorrhagic stroke, livedo reticularis, and systemic vasculopathy resembling polyarteritis nodosa 32. Additionally, hematological manifestations including hypogammaglobulinemia, pure red cell aplasia, and neutropenia are increasingly recognized 2. TNF-inhibitors effectively control vasculitic manifestations, while hematopoietic stem cell transplantation addresses severe hematological involvement 1. However, the intracellular pathophysiologic mechanisms remain incompletely understood 54.