SHANK- associated RH domain-interacting protein (SHARPIN) is a multifunctional protein associated with numerous physiological functions and many diseases. The primary role of the protein as a LUBAC-dependent component in regulating the activation of the transcription factor NF-κB accounts to its role in inflammation and antiapoptosis. Hence, an alteration of SHARPIN expression or genetic mutations or polymorphisms leads to the alteration of the above-mentioned primary physiological functions contributing to inflammation-associated diseases and cancer, respectively. However, there are complications of targeting SHARPIN as a therapeutic approach, which arises from the wide-range of LUBAC-independent functions and yet unknown roles of SHARPIN including neuronal functions. The identification of SHARPIN as a postsynaptic protein and the emerging studies indicating its role in several neurodegenerative diseases including Alzheimer’s disease suggests a strong role of SHARPIN in neuronal functioning. This review summarizes the functional roles of SHARPIN in normal physiology and disease pathogenesis and strongly suggests a need for concentrating more studies on identifying the unknown neuronal functions of SHARPIN and hence its role in neurodegenerative diseases.

SHANK 相关 RH 结构域相互作用蛋白 (SHARPIN) 是一种与多种生理功能和多种疾病相关的多功能蛋白。该蛋白质作为 LUBAC 依赖性成分在调节转录因子 NF-κB 激活中的主要作用是其在炎症和抗细胞凋亡中的作用。因此，SHARPIN 表达或基因突变或多态性的改变导致上述分别导致炎症相关疾病和癌症的主要生理功能的改变。然而，将 SHARPIN 作为一种治疗方法存在并发症，这源于广泛的 LUBAC 独立功能和 SHARPIN 的未知作用，包括神经元功能。将 SHARPIN 鉴定为突触后蛋白，以及表明其在包括阿尔茨海默病在内的多种神经退行性疾病中的作用的新兴研究表明 SHARPIN 在神经元功能中的重要作用。本综述总结了 SHARPIN 在正常生理学和疾病发病机制中的功能作用，并强烈建议需要集中更多的研究来识别 SHARPIN 的未知神经元功能，从而确定其在神经退行性疾病中的作用。