Slc31a1, also known as CTR1, encodes a protein functioning as a homotrimer for dietary copper uptake [4,5]. As an important copper transporter in the cell membrane, it influences copper homeostasis, which is crucial for maintaining the activity of enzymes and the function of transcription factors [5,7]. Copper is involved in multiple biological processes, and thus, Slc31a1 is of great biological importance. Genetic models, such as KO/CKO mouse models, can be valuable for studying its functions.

In cardiac fibrosis, fibroblast-specific Slc31a1 deficiency enhances mitochondrial copper depletion, augments glycolysis, promotes fibroblast proliferation, and triggers cardiac fibrosis [3]. In cisplatin-induced acute kidney injury, SLC31A1 knockdown can partially counteract cisplatin-induced cell death, mitochondrial dysfunction, and oxidative stress, indicating its role in exacerbating the injury through mitochondrial dysfunction [8]. In diabetic myocardial injury, excessive AGEs and copper upregulate the ATF3/SPI1/SLC31A1 signaling, disturbing copper homeostasis and promoting cuproptosis [1]. In diabetic retinopathy, SLC31A1 is upregulated, and it may be regulated by STAT1, potentially playing a role in the development of the disease [6]. In breast cancer, high SLC31A1 expression predicts poor prognosis and is related to deregulated immune response and metabolic pathways, and low SLC31A1 level predicts sensitivity to CTLA4 inhibitors but poor response to paclitaxel [2]. Pan-cancer analysis shows that SLC31A1 expression is significantly different between tumors and normal tissues in nine cancer types, and its expression is linked to immune cell infiltration, immune checkpoint genes, and immunotherapy markers [4]. Also, in multiple tumor types, SLC31A1 expression is associated with disease prognosis and immune cell infiltration in tumor tissues [9].

In conclusion, Slc31a1 is essential for copper homeostasis and plays significant roles in various biological processes and disease conditions. Model-based research, especially through KO/CKO mouse models, has revealed its functions in cardiac fibrosis, acute kidney injury, diabetes-related complications, and cancer. Understanding Slc31a1 provides insights into the mechanisms of these diseases and potential therapeutic targets.