Hematopoietic progenitor kinase 1 (HPK1) is a 97 kDa serine/threonine protein kinase expressed only in hematopoietic cells and tissues. HPK1 is comprosed of a STE20– like kinase domain in its N-terminus, four proline-rich motifs (-P-x-x-P-), a caspase cleavage site, and a distal C-terminal Citron homology domain. The proline-rich motifs are capable of binding proteins that contain SH3 domains. HPK1 is involved in many cellular signaling cascades that include MAPK signaling, antigen receptor signaling, apoptosis, growth factor signaling, and cytokine signaling. HPK1 binds many adaptor proteins including members of the Grb2 family, Nck family, Crk family, SLP-76 family, and actin-binding adaptors. HPK1 contains 13 potential tyrosine phosphorylation residues, some of which may be phosphorylated by ZAP-70, which provide potential docking sites for SH2 domains containing proteins. HPK1 is activated by both EGF and PDGF stimulation where adaptor proteins are involved in mediating the localization of effector molecules to cell surface receptors. Activation-induced cell death (AICD)-resistant T cells contain full-length HPK1, while AICDsensitive T cells have HPK1-C (cleaved form). HPK1 might be a possible molecular switch used to discriminate between the extrinsic pathway involving death receptors and the intrinsic pathway determined by the ratio between antiand pro-apoptotic Bcl-2 family members.