SERPINA12 (vaspin) is an adipokine-class serine protease inhibitor primarily expressed in white adipose tissue that modulates metabolic homeostasis by inhibiting kallikrein 7 (KLK7) 1. As an endocrine molecule, SERPINA12 regulates insulin sensitivity and glucose tolerance, with expression positively correlated to body mass index 2. The protein functions as a compensatory response to diminished insulin signaling in obesity, suggesting therapeutic potential for obesity-related insulin resistance and inflammation 2. SERPINA12 is heavily glycosylated at three asparagine residues near its reactive center loop, modifications that preserve protease inhibitory function while modulating heparin binding and thermal stability 3. Beyond metabolic regulation, loss-of-function variants in SERPINA12 cause autosomal recessive diffuse palmoplantar keratoderma, a hereditary skin disorder characterized by transgressive hyperkeratosis since childhood 4. The phenotype mirrors SERPINB7-related disease, suggesting shared mechanistic involvement in epidermal proteolytic homeostasis 4. Elevated serum SERPINA12 levels are associated with psoriatic arthritis, and decreased skin expression promotes keratinocyte inflammation and barrier dysfunction 5. Additionally, circulating extracellular vesicle-associated SERPINA12 appears enriched in pancreatic ductal adenocarcinoma, contributing to diagnostic biomarker panels 6.