Studies have shown that the expression levels of VICs phosphorylated IRE-1,PERK,eIF2α, ATF4 and RUNX2 in CAVD patients were down-regulated to varying degrees after the addition of TUDCA (28), which confirmed that ER stress is involved in valvular osteogenesis, and er stress inhibitors can inhibit ER stress and valvular osteogenesis. This evidence concerns the gene ATF4 and congenital bilateral aplasia of vas deferens from CFTR mutation.