MS4A6E (membrane spanning 4-domains A6E) is a member of the MS4A gene family clustered on chromosome 11, encoding a cell surface protein with structural similarity to CD20 and FcεRIβ 1. Unlike other MS4A family members, MS4A6E contains only two transmembrane domains rather than four and shows rare transcript expression that is not detected in hematopoietic cells or most nonlymphoid tissues 1. The protein is predicted to function as a component of oligomeric cell surface complexes involved in signal transduction, consistent with its classification in the cell surface receptor signaling pathway 1. MS4A6E has significant disease relevance, particularly in Alzheimer's disease (AD), where genetic variants in the MS4A4/MS4A6E locus have been identified as risk factors for late-onset AD through multiple genome-wide association studies 23. The gene shows differential expression in adipose tissue across PCOS mouse models and in women with PCOS, suggesting a conserved metabolic function 4. In AD research, MS4A6E exhibits sex-specific associations with cognitive decline and shows protein-protein interactions with other AD-associated genes including PICALM, BIN1, and CD2AP 56. The clinical significance lies in its potential as a therapeutic target for neurodegenerative diseases.