The SLC3A2 gene (Solute Carrier Family 3 Member 2), also known as CD98hc or 4F2hc, is ubiquitously expressed across many tissues and is often upregulated in various cancers, including lung, breast, and colorectal cancer. It encodes the cell-surface, transmembrane heavy chain of a heterodimeric amino acid transporter complex, which is covalently bound via disulfide bonds to a light chain from the SLC7A family (e.g., SLC7A5/LAT1 or SLC7A11/xCT). The primary function of the encoded protein is to act as a chaperone necessary for the light chain's proper plasma membrane localization and stability. The resulting functional complex transports specific essential amino acids; for instance, the SLC3A2/SLC7A5 dimer transports L-type neutral amino acids, while the SLC3A2/SLC7A7 dimer transports dibasic amino acids. This nutrient uptake is crucial for cell growth and metabolic reprogramming ^[1]. Beyond its transport role, SLC3A2 independently modulates integrin-dependent signaling pathways, affecting processes like cell spreading, adhesion, migration, and proliferation, which links it closely to cancer progression ^[2]. Cellular tissues with notable expression include trophoblasts (placenta), kidney proximal tubular cells, glandular cells (breast), Sertoli cells (testis), and various immune cells. SLC3A2 is primarily associated with cancer, where it acts as an oncoprotein and prognostic marker. It is also involved in specific cell death pathways like disulfidptosis ^[3]. Genetic associations have also been suggested between the SLC3A2 locus and conditions like schizophrenia, vitiligo, and Ulcerative Colitis, highlighting its broader role in cellular homeostasis ^[4]. huCD98HC(SLC3A2) mouse is a humanized model generated using gene editing technology, in which the mouse Slc3a2 endogenous extracellular domain is replaced with the human SLC3A2 extracellular domain. The murine cytoplasmic domain and transmembrane domain are preserved. This model can be used for research related to cancer, amino acid transport and metabolic intervention, immune regulation and autoimmunity, as well as the development of SLC3A2-targeted drugs.