Many of the immunoglobulin superfamily (IgSF) molecules play pivotal roles in cell communication. The Sidekick (Sdk) gene, first described in Drosophila, encodes the single-pass transmembrane protein, Sdk, which is one of the largest among IgSF membrane proteins. Sdk first appeared in multicellular animals during the Precambrian age and later evolved to Sdk1 and Sdk2 in vertebrates by gene duplication. In flies, a single Sdk is involved in positioning photoreceptor neurons and their axons in the visual system and is responsible for dynamically rearranging cell shapes by strictly populating tricellular adherens junctions in epithelia. In vertebrates, Sdk1 and Sdk2 are expressed by unique sets of cell types and distinctively participate in the formation and/or maintenance of neural circuits in the retina, indicating that they are determinants of synaptic specificity. These functions are mediated by specific homophilic binding of their ectodomains and by intracellular association with PDZ scaffold proteins. Recent human genetic studies as well as animal experiments implicate that Sdk genes may influence various neurodevelopmental and psychiatric disorders, such as autism spectrum disorders, attention-deficit hyperactivity disorder, addiction, and depression. The gigantic Sdk1 gene is susceptible to erratic gene rearrangements or mutations in both somatic and germ-line cells, potentially contributing to neurological disorders and some types of cancers. This review summarizes what is known about the structure and roles of Sdks.

许多免疫球蛋白超家族（IgSF）分子在细胞通讯中起关键作用。的搭档 （sdk）基因，首先在 果蝇编码单程跨膜蛋白Sdk，它是IgSF膜蛋白中最大的蛋白之一。 sdk 最早出现在前寒武纪时期的多细胞动物中，后来演变为 sdk1 和 SDK2在脊椎动物中通过基因复制。苍蝇sdk参与视觉系统中感光神经元及其轴突的定位，并通过严格填充上皮细胞中的三细胞粘附连接来动态重新排列细胞形状。在脊椎动物中sdk1 和 SDK2它们通过独特的细胞类型集表达，并明显参与视网膜神经回路的形成和/或维持，表明它们是突触特异性的决定因素。这些功能通过其胞外域的特异性同源结合以及与PDZ支架蛋白的细胞内缔合来介导。最近的人类遗传学研究和动物实验暗示sdk基因可能影响各种神经发育和精神疾病，例如自闭症谱系障碍，注意力缺陷多动障碍，成瘾和抑郁。巨大的sdk1该基因易受体细胞和种系细胞中不稳定的基因重排或突变影响，可能导致神经系统疾病和某些类型的癌症。这篇综述总结了有关Sdks的结构和作用的知识。