The Slc3A2 (4F2; 4F2HC; 4F2hc; 4T2HC; CD98; CD98hc; MDU1; NACAE; SSRP1) accessory protein of 630 aas. It facilitates transport of amino acids and polyamines (putrescine/spermidine) (Uemura et al. 2008). 4F2hc stabilizes GLUT1 (2.A.1.1.28) and increase glucose transport activity (Ohno et al., 2011).  It forms a heterodimer with glycoprotein CD98 (LAT1; SLC7A5), and contributes to tumorigenesis (Estrach et al. 2014).  CD98hc also modulates integrin signaling, plays a role in cell-to-cell fusion, and is essential for Brucella infection (Keriel et al. 2015). Hepatitis C virus (HCV) exploits SLC3A2 for viral propagation, and upregulation of SLC3A2 may contribute to HCV-mediated pathogenesis (Nguyen et al. 2018). ZEB1, a transcriptional repressor (P37275), promotes chemoresistance to cisplatin in ovarian cancer cells by suppressing SLC3A2 (Cui et al. 2018). SLC3A2/CD98hc and its light chain subunits constitute the heterodimeric transmembrane complexes that mediate amino acid transport and regulate MTOR and macroautophagy/autophagy (Digomann et al. 2019). It forms a tight complex with beta1 integrin (TC# 9.B.87.1.8) and TrpV4 (TC# 1.A.4.2.5) in focal adhesions where mechanochemical conversion takes place. CD98hc knock down inhibits TRPV4-mediated calcium influx induced by mechanical forces, but not by chemical activators, thus confirming the mechanospecificity of this signaling response. Molecular analysis revealed that forces applied to beta1 integrin must be transmitted from its cytoplasmic C-terminus via the CD98hc cytoplasmic tail to the ankyrin repeat domain of TRPV4 in order to produce ultra-rapid, force-induced, channel activation within the focal adhesion (Potla et al. 2020). CD98hc is an antibody drug-conjugate target in triple negative breast cancer (Montero et al. 2022). N-glycosylation is crucial for trafficking and stability of SLC3A2 (Console et al. 2022). CD98 defines a metabolically flexible, proinflammatory subset of low-density neutrophils in systemic lupus erythematosus (Martin et al. 2023).  RNA-binding protein SLC3A2 regulates melanocyte ferroptosis (Zhang et al. 2024). The non-natriuretic-dependent Xc- is composed of two protein subunits, SLC7A11 and SLC3A2, with SLC7A11 serving as the primary functional component responsible for cystine uptake and glutathione biosynthesis. SLC7A11 is implicated in tumor development through its regulation of redox homeostasis, amino acid metabolism, modulation of immune function, and induction of programmed cell death. Jiang and Sun 2024 summarized the structure and biological functions of SLC7A11, and the structure and mechanisms of transport of human Asc1/CD98hc amino acid transporterhave been reported, revealing determined at 3.4-3.8 Å resolution, revealing an inward-facing semi-occluded conformation with Ser 246 and Tyr 333 being essential for Asc1/CD98hc substrate selectivity and for the exchange and facilitated diffusion modes of transport. (Rullo-Tubau et al. 2024). α-2,3 sialyltransferases ST3GAL1 and ST3GAL2 and corresponding α-2,3-linked sialosides are upregulated in melanoma, and targets of ST3GAL1 and ST3GAL2 are enriched in transmembrane proteins involved in growth signaling, including the amino acid transporter, SLC3A2/CD98hc (Agrawal et al. 2024). The 4F2hc (Slc3a2) gene is expressed differentially in rat Alzheimer's Disease (Puris et al. 2022). The SSRP1/SLC3A2 protein plays a role in arginine transport and is a target for overcoming immune evasion and tumor progression in  peripheral T-cell lymphoma (Ren et al. 2025).