These findings indicate coordinated alterations in vesicular transport, ER stress-related processes, and inflammatory signaling in RA immune cells.<h4>Conclusions</h4>This integrative multi-omics analysis characterizes coordinated alterations of the ER-Golgi axis in RA immune cells and highlights candidate regulatory nodes, including SEC16A phosphorylation sites, RPS3, and major kinase hubs. Here, RPS3 is linked to rheumatoid arthritis.