Serpina12, also known as vaspin (visceral adipose tissue-derived serine protease inhibitor), is an adipokine. It belongs to the serpin family and functions as a serine protease inhibitor. Serpina12 is associated with multiple biological processes, including lipid metabolism, angiogenesis, inflammation, and reproduction, and is involved in hormonal homeostasis as an adipokine secreted by white adipose tissue [2,3].

In hepatocellular carcinoma (HCC), Serpina12 is preferentially overexpressed in epithelial HCC CD133 + cells. It promotes the tumorigenic capacity of HCC stem cells through hyperactivation of the AKT/β-catenin signaling cascade. Intravenous administration of rAAV8-shSerpina12 sensitized HCC cells to sorafenib and impeded the cancer stem cell subset in an immunocompetent HCC mouse model, revealing its role in HCC initiation and progression [1]. In addition, loss-of-function variants in Serpina12 underlie autosomal recessive palmoplantar keratoderma. SERPINA12 downregulation in three-dimensional skin equivalents was associated with marked epidermal acanthosis and hyperkeratosis, and decreased SERPINA12 expression led to reduced inhibition of kallikrein 7 activity and decreased levels of desmoglein-1 and corneodesmosin, important for normal epidermal differentiation [4].

In conclusion, Serpina12 plays crucial roles in multiple biological functions, especially in adipose-related hormonal regulation. The use of mouse models in studies, such as the immunocompetent HCC mouse model and three-dimensional skin equivalent models, has revealed its significant contributions to diseases like HCC and palmoplantar keratoderma, highlighting its potential as a therapeutic target in these disease areas.