Tim-3 proteins are members of the T cell immunoglobulin and mucin domain (Tim) family, which contains a group of type I transmembrane proteins expressed by innate and adaptive cell types within the immune system. In humans and other mammals, the Tim family consists of three proteins (TIM-1, -3, and -4). The signature feature of Tim proteins is the extracellular domain, which consists of an N-terminal immunoglobulin variable region-like (IgV) domain containing approximately 100 amino acids and a serine/threonine-rich mucinoid domain of varying lengths containing target sites for O- and N- binding glycosylation. To date, the IgV domain of Tim-3 has been shown to interact with phosphatidylserine, the alarm protein HMGB1 (high mobility frame 1), and galactosin-9 displayed on apoptotic cell surfaces, a widely expressed soluble protein that is specific to carbohydrate chains containing beta-galactosidine sugars. Tim-3 binding to phosphatidylserine mediates uptake of apoptotic cells by phagocytes expressing Tim-35. Recent studies using human primary CD8 T cells have shown that Tim-3 is associated with immune synapses formed between CD8 T cells and target cells, and that Tim-3 colocalizes with phosphatases that inhibit T cell receptor (TCR) signaling.