It has been well known that some species of lizard have the exceptional ability, that is ‘caudal autotomy’, as the anti-predation mechanism. After the amputation was occurred, they regenerate their new tail in a few days. The new tail section is generally shorter than the original and is composed of cartilage rather than vertebrae bone, and the skin of the regenerated tail distinctly differs from its previous appearance. We performed a proteomics analysis in extracts-derived from regenerating lizard tail tissue after amputation and found the ENPL (Endoplasmin, GRP94) as the main factor among the proteins of which up-regulated expression during regeneration. In fact, ENPL has been known to affect cell survival or proliferation. Thus, we performed farther experiments to verify that ENPL could induce chondrogenesis of mesenchymal stem cells. Mesenchymal stem cells (MSCs) are capable of differentiating into some specific cells and have self-renewal ability. Although MSCs can obtained from various tissue, the MSCs derived from tonsil tissues (Tonsil-derived Mesenchymal Stem Cells, T-MSCs) have several advantages including superior proliferation rate and differentiation capabilities, compared with MSCs derived from other tissues. In this study, we found ENPL is involved in chondrogenic differentiation of T-MSCs through suppression of ERK phosphorylation.