Peptidyl-tRNA hydrolase 2 (PTRH2; Bit-1; Bit1) is an underappreciated regulator of adhesion signals and Bcl2 expression. Its key roles in muscle differentiation and integrin-mediated signaling are central to the pathology of a recently identified patient syndrome caused by a cluster of Ptrh2 gene mutations. These loss-of-function mutations were identified in patients presenting with severe deleterious phenotypes of the skeletal muscle, endocrine, and nervous systems resulting in a syndrome called Infantile-onset Multisystem Nervous, Endocrine, and Pancreatic Disease (IMNEPD). In contrast, in cancer PTRH2 is a potential oncogene that promotes malignancy and metastasis. PTRH2 modulates PI3K/AKT and ERK signaling in addition to Bcl2 expression and thereby regulates key cellular processes in response to adhesion including cell survival, growth, and differentiation. In this Review, we discuss the state of the science on this important cell survival, anoikis and differentiation regulator, and opportunities for further investigation and translation. We begin with a brief overview of the structure, regulation, and subcellular localization of PTRH2. We discuss the cluster of gene mutations thus far identified which cause developmental delays and multisystem disease. We then discuss the role of PTRH2 and adhesion in breast, lung, and esophageal cancers focusing on signaling pathways involved in cell survival, cell growth, and cell differentiation.

肽基-tRNA水解酶2（PTRH2；位1；位1）是粘附信号和Bcl2表达的一个未得到充分认识的调节剂。它在肌肉分化和整合素介导的信号传导中的关键作用是由Ptrh2簇引起的最近发现的患者综合征的病理学的关键基因突变。这些功能丧失突变是在表现出骨骼肌，内分泌和神经系统严重有害表型的患者中发现的，这些患者导致了称为小儿发作多系统神经，内分泌和胰腺疾病（IMNEPD）的综合征。相反，在癌症中，PTRH2是潜在的致癌基因，可促进恶性肿瘤和转移。PTRH2不仅调节Bcl2表达，还调节PI3K / AKT和ERK信号传导，从而响应包括细胞存活，生长和分化在内的粘附，调节关键的细胞过程。在这篇综述中，我们讨论了关于这一重要细胞存活，失语和分化调节剂的科学现状，以及进一步研究和翻译的机会。我们从结构，法规，和PTRH2的亚细胞定位。我们讨论了迄今为止确定的导致发育延迟和多系统疾病的基因突变簇。然后，我们讨论PTRH2和黏附在乳腺癌，肺癌和食道癌中的作用，重点是参与细胞存活，细胞生长和细胞分化的信号通路。