LAUSR

GPS (MIM 139090) is an autosomal recessive disorder associated with macrothrombocytopenia, splenomegaly, myelofibrosis, heterogeneous bleeding, and defective platelet a-granules.2 The gene mutated inGPS encodes the neurobeachinlike 2 (Nbeal2) protein, which is 1 of 9 Beige and Chediak-Higashi (BEACH) domain– containing proteins (BDCPs).3 The BEACH domain (;300 amino acids) was named for the charter family member lysosomal trafficking regulatory/Chediak-Higashi syndrome 1 (LYST/CHS1) protein, which is defective in the Beige mouse and in human Chediak-Higashi syndrome. Most BDCPs also contain membrane-binding domains (eg, pleckstrin homology [PH] or Fab1, YOTB, Vac1, and EEA1 [FYVE] zinc fingers) and domains that support multiprotein complex formation (WD40 repeats). BDCPs are physiologically critical, because mutations in 4 of them cause autosomal recessive diseases. They are linked to several membrane-relatedprocesses (eg, lysosome size regulation, synaptosome formation, cilium maintenance, and autophagy). In platelets, LYST and Nbeal2 are needed for dense and a-granule biogenesis, respectively.Despiteourwealthof knowledge, the identity of specific BDCP-interacting partners and their mechanisms of action remain unclear.