T-cell activation requires 2 signals antigen by the T-cell receptor (see TCR; MIM 186880) and a costimulatory signal provided primarily by CD28 (MIM 186760) in naive T cells. HSH2 is a target of both of these signaling pathways (Greene et al., 2003
Shapiro, Chen, Shapiro: "The carboxyl-terminal segment of the adaptor protein ALX directs its nuclear export during T cell activation." in: The Journal of biological chemistry, Vol. 280, Issue 46, pp. 38242-6, (2005) (PubMed).