||The TIM (T cell/transmembrane, immunoglobulin and mucin) family plays a critical role in regulating immune responses, including allergy, asthma, transplant tolerance, autoimmunity and the response to viral infections. The unique structure of TIM immunoglobulin variable region domains allows highly specific recognition of phosphatidylserine (PtdSer), exposed on the surface of apoptotic cells. TIM-4 (T cell; immunoglobulin; Mucin-4), also known as SMUCKLER, is a 60 kDa member of the TIM family of immune regulating proteins. TIM-4 is exclusively expressed on antigen-presenting cells, where it mediates phagocytosis of apoptotic cells and plays an important role in maintaining tolerance. TIM-4 binds specifically to TIM-1 which is also the cellular receptor for the hepatitis A virus, and has been implicated in the development of asthma. Among hematopoietic cells, TIM-1 is expressed on activated B and T cells, preferentially in the Th2 subset of CD4+ T cells. The interaction of TIM-4 with TIM-1 induces costimulatory and hyperproliferative signals in T cells.