PQBP1 (polyglutamine binding protein-1) is the earliest identified molecule among the group of disease-related intrinsically disordered/denatured proteins. PQBP1 interacts with splicing-related factors via the disordered/denatured domain and regulates post-transcriptional gene expression. The mutations cause intellectual disability due to decreased dendritic spines and abnormal expression of synapse molecules in neurons, and microcephaly due to elongated cell cycle time and abnormal expression of cell cycle proteins in neural stem progenitor cells. Meanwhile, PQBP1 interacts with polyglutamine tract sequences translated from CAG triplet disease genes via their disordered/denatured structures. The second hit on PQBP1 by such neurodegenerative disease proteins is supposed to similarly impair synapse functions in neuron and proliferation of stem cells. The alteration of gene expression profile and consequently induced phenotypes of neuron and stem cells via secondary impairment of the intrinsically disordered/denatured protein PQBP1, which are similar to developmental disorders by PQBP1 gene mutations, could be a part of the main pathologies shared by multiple neurodegenerative diseases.

PQBP1（聚谷氨酰胺结合蛋白-1）是疾病相关的内在无序/变性蛋白中最早鉴定出的分子。PQBP1通过无序/变性域与剪接相关因子相互作用，并调节转录后基因表达。由于树突棘的减少和突触分子在神经元中的异常表达，这些突变导致智力残疾；由于延长的细胞周期时间和神经干祖细胞中的细胞周期蛋白的异常表达，导致小头畸形。同时，PQBP1通过其无序/变性结构与从CAG三联体疾病基因翻译的聚谷氨酰胺束序列相互作用。这种神经退行性疾病蛋白对PQBP1的第二次打击被认为同样会损害神经元中的突触功能和干细胞的增殖。通过内在的无序/变性蛋白PQBP1的继发性损伤，基因表达谱的改变以及由此诱导的神经元和干细胞表型的改变，类似于由PQBP1基因突变引起的发育障碍，可能是多种神经变性所共有的主要病理学的一部分疾病。