SURF4 is an endoplasmic reticulum (ER) transmembrane cargo receptor that plays a critical role in protein secretion and lipid homeostasis. The protein mediates the export of diverse cargoes from the ER to the Golgi apparatus via COPII-coated vesicles, including lipoproteins bearing APOB and APOA1, PCSK9, erythropoietin, and serum amyloid A1 123. SURF4 functions by recruiting different SEC24 cargo adaptor paralogs of the COPII coat to export different cargo types, with some cargoes binding co-translationally to SURF4 via a luminal pocket 4. The protein synergizes with the GTPase SAR1B to mediate transport of circulating lipoproteins, and hepatic inactivation of either SAR1B or SURF4 depletes plasma lipids and protects mice from atherosclerosis 1. SURF4 also participates in retrograde transport, facilitating STING homeostasis by mediating its retrieval from the Golgi to the ER 5. Beyond lipid metabolism, SURF4 influences liver fibrosis by controlling SAA1 secretion and hepatic stellate cell activation 2. The protein has emerged as a promising therapeutic target, with its expression linked to cancer progression and immune regulation 67.