SLP76 (SH2 domain-containing leukocyte protein of 76 kDa) is a cytosolic adaptor protein which translocates to the plasma mambrane and is involved in multiple signaling pathways in T cells, mast cells, neutrophils and platelets; B cells express its analog SLP65/BLNK (B cell linker protein). SLP76 is phosphorylated by Syk-family and Tec-family tyrosine kinases and couples them to the phosphorylation and activation of PLC-gamma. Via Gads or Grb2, SLP76 also associates with LAT adaptor by involvement of SLP76 proline-rich region. The SH2 domain of SLP76 has been identified as the region involved in binding the serine/threonine kinase HPK1. HPK1 may act as both a positive and a negative regulator by promoting the Jnk-mitogen activated protein kinase (MAPK) pathway and inhibiting the pathway leading to AP-1 activation.