MS4A4A
Membrane spanning 4-domains A4A
Also known as: MS4A4A, MS4A4
Biology & Mechanism
MS4A4A is a member of the membrane-spanning 4-domains family expressed on microglia. Variants in the MS4A gene cluster are significantly associated with Alzheimer's disease risk and with soluble TREM2 (sTREM2) levels in CSF. MS4A4A co-localizes with TREM2 at the cell surface and modulates TREM2 shedding, thereby influencing sTREM2 levels that may serve as biomarkers of microglial engagement.
Open Questions
- —What is the precise mechanism by which MS4A4A modulates TREM2 shedding?
- —Does MS4A4A have independent functions beyond regulation of TREM2 surface availability?
- —Can MS4A4A be targeted to tune sTREM2 levels as a pharmacodynamic approach?
Sources
- The MS4A gene cluster is a key modulator of soluble TREM2 and Alzheimer's disease risk (2020)
Last reviewed: June 1, 2026