Heparin-binding growth-associated molecule (HB-GAM), also known as pleiotrophin (PTN), is a highly conserved extracellular matrix-associated protein involved in various developmental processes, including the formation and plasticity of neuronal connections. PTN, identified as a novel heparin-binding, developmentally regulated cytokine, has been referred to by multiple names, including heparin-binding brain mitogen (HBBM), heparin-binding growth factor-8 (HBGF-8), heparin-binding neurite-promoting factor, heparin-binding neurotrophic factor (HBNF), heparin-affinity regulatory peptide (HARP), osteoblast-specific factor (OSF-1), and pleiotrophin. PTN is a member of a family of heparin-binding proteins sharing sequence, structural, and functional similarities. It can be used as an attachment substrate to stimulate neurite outgrowth in mixed cultures of embryonic brain cells from rats, mice, or chickens. PTN has been shown to transform NIH-3T3 and SW-13 cells, demonstrated by anchorage-independent growth and tumor formation in nude mice. These findings suggest that, despite conflicting reports of PTN's growth-promoting activity in vitro, it may play a role in abnormal cell growth in vivo.