Surf4,cargo trafficking,lipid metabolism,and therapeutic implications

Surfeit 4 is a polytopic transmembrane protein that primarily resides in the endoplasmic reticulum(ER)membrane.It is ubiquitously expressed and functions as a cargo receptor,mediating cargo transport from the ER to the Golgi apparatus via the canonical coat protein complex Il(CoPll)-coated vesicles or specific vesicles.It also participates in ER-Golgi protein trafficking through a tubular network.Meanwhile,it facilitates retrograde transportation of cargos from the Golgi apparatus to the ER through Coplcoated vesicles.Surf4 can selectively mediate export of diverse cargos,such as PCSK9 very low-density lipoprotein(VLDL),progranulin,α1-antitrypsin,STING,proinsulin,and erythropoietin.It has been implicated in facilitating VLDL secretion,promoting cell proliferation and migration,and increasing replication of positive-strand RNA viruses.Therefore,Surf4 plays a crucial role in various physiological and pathophysiological processes and emerges as a promising therapeutic target.However,the molecular mechanisms by which Surf4 selectively sorts diverse cargos for ER-Golgi protein trafficking remain elusive.Here,we summarize the most recent advances in Surf4,focusing on its role in lipid metabolism.