Surfeit locus protein 4 (SURF4)

Surfeit locus protein 4 (SURF4) is a conserved, polytopic integral membrane protein of approximately 269 amino acids (∼30 kDa) located predominantly in the endoplasmic reticulum (ER)[6]. It functions as a cargo receptor, mediating the selective export of soluble cargo proteins from the ER to the Golgi apparatus via coat protein complex II (COPII)-coated vesicles or tubular carriers[1][2][3][6]. SURF4 recognizes secretory proteins bearing a specific three-amino-acid N-terminal "ER-ESCAPE motif," enabling them to enter the secretory pathway efficiently[1][4][7]. It regulates trafficking and secretion of diverse proteins, notably those implicated in lipid metabolism (such as PCSK9 and very low-density lipoprotein, VLDL), endocrinology (proinsulin, erythropoietin), and cell signaling[1][4][7]. SURF4 is necessary for maintaining ERGIC and Golgi apparatus architecture through multiprotein complexes with other cargo receptors (e.g., ERGIC-53, p24 family members)[5]. Liver-specific knockout of SURF4 reduces plasma lipids and protects against atherosclerosis in mice, indicating its potential as a therapeutic target for metabolic disorders[1][3]. However, broad inhibition may yield wide-reaching effects on general secretion and cell viability[1][3].

Other names

Surfeit 4SURF-4ERV29FLJ22993MGC102753surfeit locus protein 4surface 4 integral membrane protein

For potential future therapies: Inhibition of SURF4 may reduce VLDL secretion and plasma cholesterol, thus reducing atherosclerosis[1][3]. Mechanistically, drugs would likely act by modulating cargo receptor function.