Post-translational tyrosine O-sulfation of proteins was first observed by Bettelheim in bovine fibrinopeptide B in 1954 (1). In the 1960s several small peptides including gastrin, phyllokinin, cholecystokinin, and caerulein were shown to be tyrosine-sulfated as well (2–5). However, the widespread occurrence of tyrosine O-sulfation was not fully appreciated until 1982, when Huttner (6) demonstrated that many proteins expressed in various mammalian cells and tissues undergo this modification. Later, Lee and Huttner (7) directly demonstrated that tyrosine O-sulfation was mediated by an enzyme, designated tyrosylprotein sulfotransferase (TPST,1 EC 2.8.2.20).