SYS1 (SYS1 golgi trafficking protein) is a multi-spanning transmembrane protein that plays a crucial role in Golgi apparatus function and intracellular protein trafficking. SYS1 forms a complex with ARFRP1 and serves as a receptor for this ARF-family GTPase at the trans-Golgi network (TGN) 1. This SYS1-ARFRP1 complex recruits ARL5, which in turn activates downstream effectors including the GARP tethering complex for retrograde transport and ARMH3 for phosphatidylinositol 4-phosphate synthesis 1. Loss of SYS1 function has widespread effects on glycan biosynthesis, deforms the Golgi apparatus, and disrupts the localization of TGN proteins 2. SYS1 is also required for proper cell surface presentation of ADAM10, affecting cellular susceptibility to bacterial toxins like Staphylococcus aureus α-hemolysin 3. Additionally, SYS1 deficiency reduces expression of glycosphingolipids including Gb3 and sphingomyelin while increasing glucosylceramide and lactosylceramide levels 2. Clinically, SYS1 has been implicated in IgA nephropathy pathogenesis through epigenetic mechanisms in B cells 4, highlighting its potential relevance in kidney disease.