CD161 is a C-type lectin-like membrane receptor expressed at high levels on NK, NKT, Th17, Mucosa Associated Invariant T cells (MAITs), non-MAIT CD8+, tissue-resident memory cells (TRMs), αβ CD4+ T cells and CD8+ T cells. CD161 levels increase when αβ T cells enter tissues. The ligand for CD161 is the lectin-like transcript 1 (LLT1). CD161/LLT1 engagement inhibits NK cell function but can inhibit or enhance αβ T cell function depending on the co-stimulatory molecules involved. The inhibitory capacity of αβ T cells can be neutralized by blocking CD161. CD161 expression on γδ T cells is associated with enhanced IFN-γ and IL-17 production and enhanced endothelial transmigration.