VNN2 is a glycosylphosphatidylinositol-anchored ectoenzyme that hydrolyzes pantetheine to recycle pantothenic acid (vitamin B5) and release cysteamine. Beyond its metabolic role, VNN2 regulates leukocyte trafficking through physical association with β2 integrin, influencing neutrophil adhesion, migration, and motility. The protein is stored in neutrophil secretory vesicles and translocates to the cell surface upon activation, where it modulates integrin avidity and triggers cytoskeletal remodeling. VNN2 has emerged as a clinically significant marker in hematologic and inflammatory diseases. In pediatric B-cell precursor acute lymphoblastic leukemia, VNN2 expression identifies patients with enhanced chemoresistance and worse prognosis, particularly those with persistent minimal residual disease 1. In primary Sjögren's syndrome, VNN2+ monocytes are significantly reduced and associate with disease markers, suggesting diagnostic utility 2. VNN2+ cells also mark monocytic myeloid-derived suppressor cells in healthy individuals, with altered expression patterns in glioma patients 3. During COVID-19, MSC infusion mobilizes a novel VNN2+ hematopoietic stem/progenitor-like population that correlates with improved clinical outcomes 4. In periodontitis, upregulated VNN2 associates with disease severity and neutrophil-mediated pathology 5. VNN2 expression is regulated transcriptionally through PKA-dependent mechanisms in ovulatory follicles, suggesting roles beyond immune function.