ILDR2 is an immunoglobulin-like transmembrane receptor with multifaceted roles in cellular regulation. As an angulin family protein, ILDR2 localizes to tricellular tight junctions where it recruits tricellulin to maintain epithelial barrier function, though it provides weaker barrier activity than related proteins LSR and ILDR1 1. In pancreatic β-cells, ILDR2 is stabilized through interaction with the ER chaperone GRP78, which prevents ubiquitin-proteasome degradation 2. ILDR2 knockdown reduces glucose-responsive insulin secretion, suggesting involvement in diabetes pathogenesis through impaired β-cell function 2. The protein functions as a B7-like immune checkpoint molecule with T-cell inhibitory activity 3. ILDR2 binds splicing factors TRA2A, TRA2B, and SRSF1 to regulate alternative pre-mRNA splicing 4, with potential roles in inner ear function where this mechanism may be relevant to hearing 5. In hepatic lipid metabolism, ILDR2 interacts with zinc finger protein ZNF70 to regulate HES1 expression and prevent hepatic steatosis 6. Recent evidence identifies ILDR2 as a novel podocyte foot process component in kidney filtration 7, while elevated ILDR2 expression correlates with late-onset Alzheimer's disease, suggesting immune modulation in neurodegeneration 8.