XKR6 (XK related 6) is a membrane protein involved in apoptotic cell clearance and immune homeostasis. Based on Gene Ontology annotations, XKR6 functions in phosphatidylserine exposure on apoptotic cell surfaces and engulfment of apoptotic cells [GO:plasma membrane, GO:apoptotic process]. XKR6 has emerged as a significant susceptibility locus for multiple autoimmune and cardiometabolic diseases. It was identified as a novel genome-wide significant risk locus for Sjögren's disease 1, and genetic variants in XKR6 are associated with childhood-onset systemic lupus erythematosus (SLE), with rs7460469 showing particularly strong association (OR = 5.58) 2. XKR6 is also implicated in shared genetic pathways between endometriosis and rheumatoid arthritis 3. Additionally, XKR6 variants influence cardiovascular and metabolic phenotypes: the rs7014968 and rs7819412 SNPs associate with altered serum lipid profiles and increased risk of coronary heart disease and ischemic stroke in Han Chinese populations 45. Recent evidence suggests XKR6 variants may be shared genetic contributors to neuroticism and tinnitus susceptibility 6. XKR6 also shows potential diagnostic value for idiopathic pulmonary fibrosis 7. These findings indicate XKR6's critical role in immune regulation and cardiovascular homeostasis, with clinical implications for understanding disease susceptibility across multiple conditions.