Tshr, the thyroid-stimulating hormone receptor gene, is crucial for thyroid function. It is a G-protein-coupled receptor that, upon binding thyroid-stimulating hormone (TSH), activates multiple signaling pathways such as the Gs/cyclic AMP and Gq/11 signaling pathways, which are essential for thyroid hormone synthesis and secretion. Post-translational modifications of Tshr, like glycosylation, phosphorylation, sialylation, and dimerization, modulate its cell-surface expression and signaling [5]. Tshr is also implicated in the regulation of immune-related processes, making it important in both normal physiological function and disease states.

In Graves' orbitopathy, Tshr is a key target antigen, and research on Tshr-inhibiting therapies is increasing, suggesting its potential as a therapeutic target [1]. In colorectal carcinoma, local TSH/Tshr signaling promotes CD8+ T-cell exhaustion and immune evasion. Conditional deletion of Tshr in CD8+ tumor-infiltrating lymphocytes (TILs) improved effector differentiation and suppressed the expression of immune checkpoint receptors through the protein kinase A (PKA)/cAMP-response element binding protein (CREB) signaling pathway [2]. The Tshr rs179247 gene polymorphism is associated with an increased risk of Graves' disease (GD) but not Hashimoto's thyroiditis (HT), indicating its potential as a biomarker for GD [3]. In congenital hypothyroidism, Tshr variants can lead to impairment of Gs/cyclic AMP and Gq/11 signaling activity, and patients with Tshr biallelic variants have a relatively mild clinical phenotype [4].

In summary, Tshr is essential for thyroid function and is involved in various disease-related processes. Research using gene-deletion models, such as the conditional deletion of Tshr in CD8+ TILs, has provided insights into its role in cancer-related immune evasion. In addition, studies on Tshr gene polymorphisms and variants have contributed to understanding its association with autoimmune thyroid diseases and congenital hypothyroidism, offering potential for disease prediction and treatment.