T cell-specific adapter protein is a relatively recently described signaling adapter molecule expressed predominantly in T cells and NK cells. Studies in mouse and man have indicated that reduced expression of TSAd in T cells may predispose toward the development of autoimmune disease. In lupus-prone TSAd-deficient mice the development of autoimmunity is associated with an impaired T cell death response to antigens in vivo. Probably, this impaired death response is consequent to reduced T cell antigen receptor (TCR)-induced synthesis of the interleukin-2 (IL-2) cytokine in TSAd-deficient T cells. TSAd appears to contribute to IL-2 synthesis at multiple different levels acting in both the nucleus and cytoplasm of T cells. Recent advances relating to the role of TSAd in T cell signal transduction and as a regulator of autoimmune responses are discussed.