To investigate the underlying molecular mechanism, we developed several models of XPNPEP3 adaptation in cells and mice and explored the impacts of c.634G>A and c.761G>T on XPNPEP3, mitochondria, and the primary cilium to better understand the role of XPNPEP3 in NPHPL1 and the connection between mitochondria and ciliopathy. This evidence concerns the gene XPNPEP3 and ciliopathy.