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CD161 is a C-type lectin-like receptor and a type II transmembrane protein, widely expressed on various lymphocytes, including natural killer （NK） cells, CD4+ T cells, CD8+ T cells, and mucosal-associated invariant T （MAIT） cells. It functions as a co-stimulatory molecule, influencing T cell receptor （TCR）-dependent responses. CD161+ T cells are enriched in the gut and exhibit enhanced cytokine production. However, the exact mechanisms of CD161 are still controversial, as it may have both promoting and inhibitory roles in T cell activation. Additionally, CD161 is associated with transcriptional and functional phenotypes across different T cell lineages, with some conserved features among these subsets.