P16 mediated cell cycle arrest and senescence (Takahashi et al., 2006), The absence of p16 activated the accumulation of Akt and cyclin D, upregulated IGF1 pathway, promoted the proliferation and regeneration of aecii, and finally effectively prevented the cigarette induced emphysema (Cottage et al., 2019). Here, CDKN2A is linked to pulmonary emphysema.