Despite these implications of Siglec-16 to counteract a dampening of inflammatory responses by the polySia-Siglec-11 axis, its interplay with Siglec-11 under physiological conditions remains to be explored and virtually nothing is known about how the presence or absence of functional Siglec-16 affects neuroinflammation after insults or in neurodegenerative diseases, or how it may modulate the immune environment of polySia-positive brain tumors1. Here, SIGLEC11 is linked to neurodegenerative disease.