English: Schematic diagram of the multiple domains of SORLA, the protein product of the SORL1 gene. The relative orientations of the domains are drawn and color-coded to match the ectodomain model of Jensen et al., PNAS (2023). The N-terminal VPS10 domain is in green; the two 10CC domains are in red; The EGF domain is in orange; the 11 CR domains are in light cyan; the 6 3Fn domains are in light blue-grey. These 21 domains comprise the extracellular or ectodomain part of the protein, which in the eindosome is located inside the trafficking tubule. the ecotodomain is followed by a single-pass transmembrane alpha helix and a short (~54-residue) C-terminal tail (SORLA is a Type I integral membrane protein). The tail projects into the cytosol, where it interacts with the VPS26 subunit of retromer, the master controller of protein trafficking out of the early endosome. Cargo proteins and peptides can bind to the VPS10 domain or the CR domains, at least. Figure from Holstege et al., medRxiv (2023) https://www.medrxiv.org/content/10.1101/2023.07.13.23292622v1.full.pdf