To summarize, our experiments identify a preferred binding pose for h-cisPT to engage with the ER membrane, making substantial membrane contacts via both Nterminal and other exposed aromatic residues on an adjacent helix. In this orientation, the nonpolar prenyl product is oriented correctly to potentially squeeze between the helices and insert into the adjacent ER membrane. However, this remains speculative and in need of further study, as spontaneous product insertion has not been observed in this work. Future simulations can probe this possibility more directly, building on the bound orientation developed here to develop further insight into the product release question in h-cisPT.