COPA syndrome is a rare monogenic disorder characterized by inflammation of the lungs, kidneys, and joints. This disorder was first recognized in 2015 [1], and to date, there have been fewer than 100 cases reported worldwide. COPA syndrome is driven by heterozygous missense mutations in the WD40 domain of the coatomer subunit α (COPα) gene, which can arise de novo or through autosomal-dominant inheritance. The COPα gene encodes the coat protein complex I (COPI), which is ubiquitously expressed in eukaryotic cells. Under normal conditions, coatomer complexes play an important role in the retrograde trafficking of cellular proteins from the Golgi apparatus to the endoplasmic reticulum (ER). COPα mutations result in defects in this system which prevent normal protein trafficking and induce compensatory increases in ER protein synthesis. This in turn leads to a pronounced ER stress response and the activation of inflammatory cascades. The resulting clinical manifestations include interstitial lung disease (ILD), diffuse alveolar hemorrhage, polyarthritis, nephritis, and autoantibody positivity [1, 2]. In addition, it has recently been shown that COPA syndrome shares features with STING-associated vasculopathy with onset in infancy (SAVI), including the activation of type I interferon-stimulated genes [3]. Furthermore, the role of COPI in STING trafficking has been highlighted by four groups (including [3]). Current treatment options are limited to corticosteroids and anti-inflammatory therapies, which provide partial symptomatic relief. In some cases, treatment can be guided by mechanism-related factors; for example, the Janus kinase inhibitors baricitinib and ruxolitinib have been utilized in some COPA syndrome patients. Despite receiving chronic treatment, most reported patients have developed pulmonary disease, with some requiring bilateral lung transplantation [4].