The VTCN1 gene, also known as B7-H4, B7S1, or B7x, encodes a protein belonging to the B7 costimulatory protein family, which is typically found on the surface of antigen-presenting cells. This protein functions as a negative regulator of T-cell-mediated immune responses by inhibiting T-cell activation, proliferation, cytokine production, and cytotoxicity, playing a crucial role in maintaining immune homeostasis, particularly in the tumor microenvironment ^[1]. While VTCN1 mRNA can be detected in various lymphoid and non-lymphoid tissues such as kidney, pancreas, liver, lung, ovary, placenta, spleen, and testis, its protein expression is often restricted in normal tissues, with notable expression on activated T- and B-cells, monocytes, and dendritic cells ^[2]. However, it is frequently overexpressed on the cell surface of various cancer cells and tumor-associated macrophages, where it contributes to immune escape. Associated diseases primarily include a wide range of cancers, such as breast, ovarian, endometrial, renal cell, non-small cell lung, pancreatic, and colorectal cancers, where high levels correlate with tumor progression and poor prognosis ^[3]. Furthermore, dysregulation of VTCN1 has also been linked to autoimmune and inflammatory diseases like rheumatoid arthritis and type 1 diabetes ^[4]. The B6-hB7-H4 (hVTCN1) mouse is a humanized model, constructed by replacing the partial extracellular domain of the endogenous mouse Vtcn1 gene with the partial extracellular domain of the human VTCN1 gene. B6-hB7-H4 (hVTCN1) mice can be used for research into the pathogenesis of various cancers, as well as autoimmune and inflammatory diseases. They are also useful for the screening, development, and safety evaluation of VTCN1-targeted drugs.