Pref-1 (also called Dlk1) is made as an EGF-repeat containing transmembrane protein that produces a biologically active soluble form by TACE mediated cleavage. Soluble Pref-1 activates the MEK/ERK pathway. In adipose tissue, Pref-1 is specifically expressed in preadipocytes but not in adipocytes, and thus is used as a preadipocyte marker. Inhibition of adipogenesis by Pref-1 has been well established in vitro as well as in vivo by ablation and overexpression of Pref-1. Sox9, a transcription factor expressed in preadipocytes to suppress C/EBP and C/EBP expression, is required to be downregulated before adipocyte differentiation can proceed. By activating MEK/ERK, Pref-1 prevents downregulation of Sox9, resulting in inhibition of adipogenesis. Furthermore, by inducing Sox9, Pref-1 promotes chondrogenic induction of mesenchymal cells but prevents chondrocyte maturation as well as osteoblast differentiation. Thus, Pref-1 directs multipotent mesenchymal cells towards the chondrogenic lineage but inhibits differentiation into adipocytes as well as osteoblasts and chondrocytes. Pref-1, encoded by an imprinted gene, has also been detected in progenitor cells in various tissues during regeneration and therefore may have a more general role in maintaining cells in an undifferentiated state.