8.A.125.1.5
Cleft lip and palate transmembrane protein 1-like protein, Clptm1L, of 538 aas and possibly 7 TMSs in a 1 (N-terminal) + 3 + 3 TMS arrangement.  It enhances cisplatin-mediated apoptosis, when overexpressed (Yamamoto et al. 2001). It is a lipid scramblase, required for efficient glycosylphosphatidylinositol biosynthesis (Wang et al. 2022). Scramblases translocate lipids across the lipid bilayer without consumption of ATP, thereby regulating lipid distributions in cellular membranes. Cytosol-to-lumen translocation across the endoplasmic reticulum (ER) membrane is a common process among lipid glycoconjugates involved in posttranslational protein modifications in eukaryotes. These translocations are thought to be mediated by specific ER-resident scramblases.  Wang et al. 2022 showed that CLPTM1L, an integral membrane protein with seven or eight putative TMSs, is the major lipid scramblase involved in efficient glycosylphosphatidylinositol biosynthesis in the ER membrane. These results validate the long-standing hypothesis that lipid scramblases ensure the efficient translocations of lipid glycoconjugates across the ER membrane for protein glycosylation pathways.