SOCS1 is a critical checkpoint in immune homeostasis, inflammation, and tumor immunity. As a member of the SOCS family, SOCS1 functions in a negative feedback loop to inhibit signaling via interferon, interleukin-12, and interleukin-2 family cytokines. These cytokines are essential for immune defense against viral pathogens and cancer. SOCS1 acts as an important immune checkpoint, as evidenced by detrimental variants in patients with cytokine-driven inflammatory and autoimmune diseases. SOCS1 also restricts anti-tumor immunity, playing a role in tumor intrinsic processes and impacting immune cell responses. This review describes the mechanism of SOCS1 action, focusing on its role in autoimmunity and cancer, and discusses potential SOCS1-directed cancer therapies to enhance adoptive immunotherapy and immune checkpoint blockade. SOCS1 inhibits the IFNγ-driven JAK-STAT pathway by binding to the JAK-GQM motif, blocking JAK enzymatic activity. SOCS1 has a nuclear localization signal, consistent with its presence in the nucleus. SOCS1 is a critical negative regulator of signaling in response to various cytokines, including type I, II, and III IFN and IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, and IL-21. It is constitutively expressed in the thymus, where it plays a vital role in T cell development and homeostasis. Under infectious challenge or inflammatory disease, SOCS1 expression is induced in response to various cytokines, enabling it to act in a classic negative feedback loop. In human disease, SOCS1 mutations are associated with immune dysregulation, autoimmune diseases, and malignancy. Patients with SOCS1 mutations exhibit a range of autoimmune diseases, including SLE, CVID, and Evans syndrome. SOCS1 is also linked to tumor suppression, with reduced SOCS1 expression correlated with poor prognosis in various cancers. SOCS1 inhibits cytokine signaling, which is critical for maintaining immune homeostasis and resolving inflammatory signaling. In cancer, SOCS1 inhibition of cytokine signaling is required to maintain immune homeostasis and resolve inflammatory signaling. SOCS1 has been shown to target various pathways, including MET receptor tyrosine kinase, p21, p53, and NF-kB. The IFNγ-SOCS1 axis and immune checkpoint blockade are important in cancer treatment. SOCS1 deficiency can lead to increased expression of immune checkpoints, sensitizing tumors to immune checkpoint blockade. SOCS1 also limits anti-tumor immunity through various immune cell types. SOCS1 has specific roles in CD4+ and CD8+ T cells, dendritic cells, and macrophages that limit anti-tumor immunity. SOCS1 is a potential negative regulator of the anti-tumor immune response. In conclusion, SOCS1 is anSOCS1 is a critical checkpoint in immune homeostasis, inflammation, and tumor immunity. As a member of the SOCS family, SOCS1 functions in a negative feedback loop to inhibit signaling via interferon, interleukin-12, and interleukin-2 family cytokines. These cytokines are essential for immune defense against viral pathogens and cancer. SOCS1 acts as an important immune checkpoint, as evidenced by detrimental variants in patients with cytokine-driven inflammatory and autoimmune diseases. SOCS1 also restricts anti-tumor immunity, playing a role in tumor intrinsic processes and impacting immune cell responses. This review describes the mechanism of SOCS1 action, focusing on its role in autoimmunity and cancer, and discusses potential SOCS1-directed cancer therapies to enhance adoptive immunotherapy and immune checkpoint blockade. SOCS1 inhibits the IFNγ-driven JAK-STAT pathway by binding to the JAK-GQM motif, blocking JAK enzymatic activity. SOCS1 has a nuclear localization signal, consistent with its presence in the nucleus. SOCS1 is a critical negative regulator of signaling in response to various cytokines, including type I, II, and III IFN and IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, and IL-21. It is constitutively expressed in the thymus, where it plays a vital role in T cell development and homeostasis. Under infectious challenge or inflammatory disease, SOCS1 expression is induced in response to various cytokines, enabling it to act in a classic negative feedback loop. In human disease, SOCS1 mutations are associated with immune dysregulation, autoimmune diseases, and malignancy. Patients with SOCS1 mutations exhibit a range of autoimmune diseases, including SLE, CVID, and Evans syndrome. SOCS1 is also linked to tumor suppression, with reduced SOCS1 expression correlated with poor prognosis in various cancers. SOCS1 inhibits cytokine signaling, which is critical for maintaining immune homeostasis and resolving inflammatory signaling. In cancer, SOCS1 inhibition of cytokine signaling is required to maintain immune homeostasis and resolve inflammatory signaling. SOCS1 has been shown to target various pathways, including MET receptor tyrosine kinase, p21, p53, and NF-kB. The IFNγ-SOCS1 axis and immune checkpoint blockade are important in cancer treatment. SOCS1 deficiency can lead to increased expression of immune checkpoints, sensitizing tumors to immune checkpoint blockade. SOCS1 also limits anti-tumor immunity through various immune cell types. SOCS1 has specific roles in CD4+ and CD8+ T cells, dendritic cells, and macrophages that limit anti-tumor immunity. SOCS1 is a potential negative regulator of the anti-tumor immune response. In conclusion, SOCS1 is an