T-cell immunoglobulin and mucin domain containing 4 receptor (TIM-4)

T-cell immunoglobulin and mucin domain containing 4 (TIM-4) is a receptor protein encoded by the TIMD4 gene[1]. It is predominantly expressed on antigen-presenting cells such as macrophages and dendritic cells, as well as on some B cells, NK T cells, mast cells, and certain tumor cells[1][3][4][8]. TIM-4 serves as a phosphatidylserine receptor, binding to phosphatidylserine exposed on apoptotic cell surfaces, thereby mediating their recognition and clearance—a process called efferocytosis[1][2][3][4][5][6]. Structurally, it contains an IgV domain critical for PS binding, a mucin domain, but lacks a canonical intracellular signaling motif; signal transduction for engulfment depends on cooperation with integrins and external signaling proteins[2][3][6]. TIM-4 is essential for maintaining tissue homeostasis, preventing autoimmunity from uncleared apoptotic debris, modulating inflammation, and shaping the immune response. Aberrant expression or function of TIM-4 is implicated in allergic diseases, cancer (tumor tolerance via reduced antigen presentation), autoimmunity, and infection[1][3][4][8]. The receptor is a promising but still experimental immunotherapy target, with several blocking antibodies in preclinical and early clinical research[1][3][8].\n\nPhosphatidylserine is not a protein nor a receptor but a phospholipid that serves as a ligand for TIM-4 and other phagocytic receptors[2][6]. In this query, the main target is TIM-4 as the receptor, with phosphatidylserine as its defining ligand.

Other names

TIMD4TIM4T-cell membrane protein 4T cell immunoglobulin and mucin domain containing 4SMUCKLER

Monoclonal antibodies/blockers: block phosphatidylserine binding and efferocytosis, modulate immune activity, affect the tumor microenvironment[1][3][8].