Human Pref-1 (preadipocyte factor 1), also known as Dlk1 and pG2, is a member of the Notch/Delta/Serrate family of EGF-like repeat-containing proteins that serve as ligands in the Notch signaling pathway. Synthesized as a 383-amino acid precursor with a 23-amino acid signal sequence, a 280-amino acid extracellular region, a 24-amino acid transmembrane segment, and a 56-amino acid cytoplasmic tail, human Pref-1's extracellular region contains six tandem EGF repeats, a juxtamembrane region, and multiple O- and N-glycosylation sites. The 50-60 kDa heterogeneous transmembrane forms of Pref-1 result from variable glycosylation. Mature human Pref-1A shares 85% amino acid identity with mouse and rat homologs. Highly expressed in 3T3-L1 preadipocytes and various endocrine tissues, including pituitary somatotrophs, insulin-producing cells, testicular Leydig cells, and ovarian theca interna and Hilus cells, Pref-1 blocks preadipocyte differentiation into mature adipocytes when constitutively expressed. It also regulates skeletal stem cell, thymocyte, and adrenal gland cell differentiation and inhibits GH secretion in pituitary GH3 cells.