TYROBP（也称为DAP12或KARAP）是一种编码跨膜信号转导蛋白的基因，属于免疫受体信号传导复合物家族。它主要表达于免疫细胞（如自然杀伤细胞、巨噬细胞、树突状细胞和某些T细胞亚群）中，通过与多种免疫受体（如TREM家族、SIRPβ1等）结合，传递激活信号。TYROBP的胞内段含有免疫受体酪氨酸激活基序（ITAM），当受体与配体结合后，ITAM被磷酸化，进而招募Syk或ZAP70等激酶，启动下游信号通路，调控免疫细胞的活化、增殖和细胞因子分泌等功能。TYROBP的突变可能导致其功能丧失，例如在Nasu-Hakola病（一种罕见的遗传性疾病）中，TYROBP或TREM2的突变会导致破骨细胞和神经小胶质细胞功能障碍，引发早发性痴呆和骨囊肿。此外，TYROBP在阿尔茨海默病中也发挥作用，其表达异常可能影响小胶质细胞的炎症反应和β-淀粉样蛋白清除能力。过表达TYROBP可能增强免疫细胞的激活，导致过度炎症反应或自身免疫疾病，而表达降低则可能削弱免疫监视功能，增加感染或肿瘤风险。TYROBP属于TREM受体信号复合物家族，该家族成员均通过ITAM传递信号，参与先天免疫和炎症调控。其共性包括依赖跨膜受体与配体结合，并通过Syk家族激酶触发下游通路，影响细胞吞噬、迁移和炎症因子释放等过程。

该基因编码含有在其胞质结构域中包含免疫受体基于酪氨酸的活化基序（ITAM）的跨膜信号多肽。所编码的蛋白质可与杀伤细胞抑制性受体（KIR）家族的膜糖蛋白的关联，并且可以作为活化的信号转导元件起作用。这种蛋白质可结合泽塔链（TCR）相关的蛋白激酶的70kDa（ZAP-70）和脾酪氨酸激酶（SYK），并起到信号转导，骨造型，脑髓鞘和炎症的作用。该基因内突变已与硬化性白质脑病（PLOSL），也被称为那须Hakola疾病多囊卵巢lipomembranous osteodysplasia相关联。其公认的受体，触发受体骨髓细胞2（TREM2）表示，也导致PLOSL。编码不同亚型多重替代转录变异体已经确定了这个基因。 [由RefSeq的，2010年3月提供]

TYROBP, also known as DAP12 or KARAP, encodes a transmembrane signaling adaptor protein that serves as a critical component of the immunoreceptor signaling complex family. Primarily expressed in innate immune cells such as natural killer cells, macrophages, dendritic cells, and specific T-cell subsets, TYROBP lacks its own ligand-binding domain but functions by non-covalently associating with various single-pass transmembrane receptors, including members of the TREM family and SIRPβ1. The intracellular domain of TYROBP contains an immunoreceptor tyrosine-based activation motif (ITAM); upon ligand engagement of the associated receptor, this motif is phosphorylated, thereby recruiting and activating Syk or ZAP70 kinases to initiate downstream signaling cascades. These pathways regulate essential cellular processes, including activation, proliferation, cytokine secretion, phagocytosis, and migration, thereby modulating both innate immune responses and inflammatory homeostasis. Genetic mutations in TYROBP can lead to loss-of-function phenotypes, most notably in Nasu-Hakola disease, a rare autosomal recessive disorder where defects in TYROBP or its partner TREM2 impair osteoclast and microglial function, resulting in early-onset dementia and bone cysts. Furthermore, TYROBP plays a significant role in neurodegenerative contexts; dysregulated expression may compromise microglial inflammatory responses and the clearance of amyloid-beta plaques, contributing to the pathogenesis of Alzheimer’s disease. Conversely, aberrant overexpression can drive excessive immune activation and autoimmunity, while reduced expression may weaken immune surveillance, increasing susceptibility to infections and tumorigenesis. As a core member of the TREM receptor signaling complex family, TYROBP exemplifies the conserved mechanism whereby ITAM-bearing adaptors translate extracellular ligand binding into intracellular kinase activation, ultimately governing cellular effector functions in health and disease.

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