Surfeit locus protein 4 of 269 aas and 8 predicted TMSs in a 4 + 4 TMS arrangement, Surf-4 or Surf4. It has amplification and increased expression in the tumor tissues of several human cancer patients. Overexpression of SURF4 leads to increased cell proliferation, migration, and maintenance of anchorage-independent growth. In addition, NIH3T3 cells overexpressing SURF4 induced tumor growth in mice (Kim et al. 2018). Surf-4, together with SAR1B (SARA2; SARB, of 198 aas and 0 TMSs; Q9Y6B6), ensures delivery of the packages to the cell membrane for secretion, and receptor-mediated ER export of lipoproteins controls lipid homeostasis in mice and humans (Wang et al. 2020). It functions as a cargo receptor, mediating cargo transport from the ER and the Golgi apparatus via the canonical coat protein complex II (COPII)-coated vesicles (Shen et al. 2022). It also participates in ER-Golgi protein trafficking through a tubular network and facilitates retrograde transport of cargos from the Golgi apparatus to the ER through COPI-coated vesicles (Shen et al. 2022). An overview of receptor-mediated transport of secretory proteins from the ER to the Golgi, with a focus on the current understanding of two mammalian cargo receptors: the LMAN1-MCFD2 complex and SURF4, has appeared (Zhang et al. 2023).