Allo-Ile-isoindoline is a competitive inhibitor of DPP8/9, but its membrane penetration is poor and its inhibitory effect on DPP8/9 in the cytoplasm is weak (Wu et al., 2009; Bank et al., 2011), the serious toxicity on cell culture and animal models in previous studies were observed, such as alopecia, thrombocytopenia, reticulocytopenia, increased mortality in animals, and attenuated human T cell activation in vitro (Lankas et al., 2005), which may be attributed to off-target effects rather than inhibition of DPP8/9 enzymatic activity. This evidence concerns the gene DPP8 and alopecia.