DAP12 (DNAX-activating protein 12), also known as KARAP or TYROBP, is a transmembrane adaptor protein critical for signaling in immune cells. It belongs to the immunoglobulin superfamily and contains a cytoplasmic immunoreceptor tyrosine-based activation motif (ITAM). DAP12 pairs with cell-surface receptors lacking intrinsic signaling domains, such as TREM (triggering receptor expressed on myeloid cells) and NK cell receptors, enabling signal transduction upon ligand binding. Upon receptor engagement, DAP12 undergoes phosphorylation at its ITAM, recruiting Syk or ZAP70 kinases to initiate downstream pathways that regulate cellular activation, cytokine production, and cytotoxicity.
DAP12 is primarily expressed in natural killer (NK) cells, macrophages, dendritic cells, and microglia. Its dysfunction is linked to diseases like Nasu-Hakola disease, a rare genetic disorder characterized by bone cysts and early-onset dementia due to DAP12 or TREM2 mutations. Aberrant DAP12 signaling is also implicated in neurodegenerative conditions (e.g., Alzheimer’s) and autoimmune disorders.
DAP12-specific antibodies are essential research tools for studying receptor interactions, signaling mechanisms, and disease pathogenesis. They enable detection of DAP12 expression, block functional activity, or assess post-translational modifications. Therapeutic antibodies targeting DAP12-associated pathways are under exploration for modulating immune responses in inflammatory and neurological diseases.